Current Knowledge and Perspectives of Immunotherapies for Neuroblastoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Barriers to Effective Immunotherapy in NBL
2.1. Immune Cells and Cytokines
2.1.1. Macrophages
2.1.2. MDSCs
2.1.3. NK Cells
2.1.4. T Cells
2.2. Stromal Cells
2.2.1. Cancer-Associated Fibroblasts (CAFs)
2.2.2. Mesenchymal Stromal Cells (MSCs)
2.2.3. Schwann Cells
2.3. Vasculature
2.4. NBL Tumor Cells and Their Intrinsic Low Immunogenicity
3. Current Immunotherapies for NBL
3.1. Therapeutic Strategies to Target Cancer Cells
Anti-GD2 Antibodies and the Derived Therapies
3.2. Therapeutic Strategies to Target Immune Cells
3.2.1. Recruitment
3.2.2. Depletion
3.2.3. Repolarization
3.2.4. Immune Checkpoint Blockade
3.3. Therapeutic Strategies to Target Other Cells
3.3.1. Cytokines and Stromal Cells
3.3.2. Vasculature
4. Recent Advances and Future Directions of Immunotherapies for NBL
4.1. Targeted Drugs
4.1.1. Anaplastic Lymphoma Kinase (ALK) Inhibitors
4.1.2. Small Extracellular Vesicles
4.1.3. Aurora Kinase A (AURKA) Inhibitors
4.2. Immunotherapy and Novel Therapeutics
CAR-T Cell Therapies
5. Conclusions
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ADC | antibody–drug conjugate |
ADCC | antibody-dependent cell cytotoxicity |
ALK | anaplastic lymphoma kinase |
Arg-2 | Arginase-2 |
AURK | aurora kinase |
AURKA | aurora kinase A |
AURKB | aurora kinase B |
CAF | cancer-associated fibroblast |
CAR | chimeric antigen receptor |
COG | Children’s Oncology Group |
DC | dendritic cell |
ERK | extracellular signal-regulated kinase |
EGFL8 | epidermal growth factor-like protein 8 |
FasL | Fas ligand |
GM-CSF | granulocyte-macrophage colony-stimulating factor |
HIF | hypoxia-inducible factor |
HMGB1 | high mobility group box-1 |
HR NBL | high-risk NBL |
ICI | immune checkpoint inhibitor |
IL | interleukin |
mAb | monoclonal antibody |
MCP | monocyte chemoattractant protein |
MDSC | myeloid-derived suppressor cell |
MHC | major histocompatibility complex |
MIF | macrophage inhibitory factor |
M-MDSC | mononuclear MDSC |
MSC | mesenchymal stromal cell |
NBL | neuroblastoma |
NGF | nerve growth factor |
NK cell | natural killer cell |
NKT | natural killer T cell |
PBMC | peripheral blood mononuclear cell |
PDGF | platelet-derived growth factor |
PMN-MDSC | polymorphonuclear MDSC |
ROS | reactive oxygen species |
sEV | small extracellular vesicle |
TAA | tumor-associated antigen |
TAM | tumor-associated macrophage |
TGF | transforming growth factor |
TIL | tumor-infiltrating lymphocyte |
TME | tumor microenvironment |
TKI | tyrosine kinase inhibitor |
Treg | regulatory T cell |
References
- Coughlan, D.; Gianferante, M.; Lynch, C.F.; Stevens, J.L.; Harlan, L.C. Treatment and survival of childhood neuroblastoma: Evidence from a population-based study in the United States. Pediatr. Hematol. Oncol. 2017, 34, 320–330. [Google Scholar] [CrossRef] [PubMed]
- Pugh, T.J.; Morozova, O.; Attiyeh, E.F.; Asgharzadeh, S.; Wei, J.S.; Auclair, D.; Carter, S.L.; Cibulskis, K.; Hanna, M.; Kiezun, A.; et al. The genetic landscape of high-risk neuroblastoma. Nat. Genet. 2013, 45, 279–284. [Google Scholar] [CrossRef] [PubMed]
- Rizvi, N.A.; Hellmann, M.D.; Snyder, A.; Kvistborg, P.; Makarov, V.; Havel, J.J.; Lee, W.; Yuan, J.; Wong, P.; Ho, T.S.; et al. Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer. Science 2015, 348, 124–128. [Google Scholar] [CrossRef]
- Cohn, S.L.; Pearson, A.D.; London, W.B.; Monclair, T.; Ambros, P.F.; Brodeur, G.M.; Faldum, A.; Hero, B.; Iehara, T.; Machin, D.; et al. The International Neuroblastoma Risk Group (INRG) classification system: An INRG Task Force report. J. Clin. Oncol. 2009, 27, 289–297. [Google Scholar] [CrossRef] [PubMed]
- DuBois, S.G.; Kalika, Y.; Lukens, J.N.; Brodeur, G.M.; Seeger, R.C.; Atkinson, J.B.; Haase, G.M.; Black, C.T.; Perez, C.; Shimada, H.; et al. Metastatic sites in stage IV and IVS neuroblastoma correlate with age, tumor biology, and survival. J. Pediatr. Hematol. Oncol. 1999, 21, 181–189. [Google Scholar] [CrossRef] [PubMed]
- Mussai, F.; Egan, S.; Hunter, S.; Webber, H.; Fisher, J.; Wheat, R.; McConville, C.; Sbirkov, Y.; Wheeler, K.; Bendle, G.; et al. Neuroblastoma Arginase Activity Creates an Immunosuppressive Microenvironment That Impairs Autologous and Engineered Immunity. Cancer Res. 2015, 75, 3043–3053. [Google Scholar] [CrossRef] [PubMed]
- Layer, J.P.; Kronmüller, M.T.; Quast, T.; van den Boorn-Konijnenberg, D.; Effern, M.; Hinze, D.; Althoff, K.; Schramm, A.; Westermann, F.; Peifer, M.; et al. Amplification of N-Myc is associated with a T-cell-poor microenvironment in metastatic neuroblastoma restraining interferon pathway activity and chemokine expression. Oncoimmunology 2017, 6, e1320626. [Google Scholar] [CrossRef]
- Wei, J.S.; Kuznetsov, I.B.; Zhang, S.; Song, Y.K.; Asgharzadeh, S.; Sindiri, S.; Wen, X.; Patidar, R.; Najaraj, S.; Walton, A.; et al. Clinically Relevant Cytotoxic Immune Cell Signatures and Clonal Expansion of T-Cell Receptors in High-Risk MYCN-Not-Amplified Human Neuroblastoma. Clin. Cancer Res. 2018, 24, 5673–5684. [Google Scholar] [CrossRef] [PubMed]
- Armstrong, A.E.; Danner-Koptik, K.; Golden, S.; Schneiderman, J.; Kletzel, M.; Reichek, J.; Gosiengfiao, Y. Late Effects in Pediatric High-risk Neuroblastoma Survivors After Intensive Induction Chemotherapy Followed by Myeloablative Consolidation Chemotherapy and Triple Autologous Stem Cell Transplants. J. Pediatr. Hematol. Oncol. 2018, 40, 31–35. [Google Scholar] [CrossRef]
- Iehara, T.; Hamazaki, M.; Tajiri, T.; Kawano, Y.; Kaneko, M.; Ikeda, H.; Hosoi, H.; Sugimoto, T.; Sawada, T. Successful treatment of infants with localized neuroblastoma based on their MYCN status. Int. J. Clin. Oncol. 2013, 18, 389–395. [Google Scholar] [CrossRef]
- Laverdière, C.; Cheung, N.K.; Kushner, B.H.; Kramer, K.; Modak, S.; LaQuaglia, M.P.; Wolden, S.; Ness, K.K.; Gurney, J.G.; Sklar, C.A. Long-term complications in survivors of advanced stage neuroblastoma. Pediatr. Blood Cancer 2005, 45, 324–332. [Google Scholar] [CrossRef] [PubMed]
- Strother, D.R.; London, W.B.; Schmidt, M.L.; Brodeur, G.M.; Shimada, H.; Thorner, P.; Collins, M.H.; Tagge, E.; Adkins, S.; Reynolds, C.P.; et al. Outcome after surgery alone or with restricted use of chemotherapy for patients with low-risk neuroblastoma: Results of Children’s Oncology Group study P9641. J. Clin. Oncol. 2012, 30, 1842–1848. [Google Scholar] [CrossRef] [PubMed]
- Twist, C.J.; Schmidt, M.L.; Naranjo, A.; London, W.B.; Tenney, S.C.; Marachelian, A.; Shimada, H.; Collins, M.H.; Esiashvili, N.; Adkins, E.S.; et al. Maintaining Outstanding Outcomes Using Response- and Biology-Based Therapy for Intermediate-Risk Neuroblastoma: A Report From the Children’s Oncology Group Study ANBL0531. J. Clin. Oncol. 2019, 37, 3243–3255. [Google Scholar] [CrossRef] [PubMed]
- Nuchtern, J.G.; London, W.B.; Barnewolt, C.E.; Naranjo, A.; McGrady, P.W.; Geiger, J.D.; Diller, L.; Schmidt, M.L.; Maris, J.M.; Cohn, S.L.; et al. A prospective study of expectant observation as primary therapy for neuroblastoma in young infants: A Children’s Oncology Group study. Ann. Surg. 2012, 256, 573–580. [Google Scholar] [CrossRef] [PubMed]
- Matthay, K.K.; Perez, C.; Seeger, R.C.; Brodeur, G.M.; Shimada, H.; Atkinson, J.B.; Black, C.T.; Gerbing, R.; Haase, G.M.; Stram, D.O.; et al. Successful treatment of stage III neuroblastoma based on prospective biologic staging: A Children’s Cancer Group study. J. Clin. Oncol. 1998, 16, 1256–1264. [Google Scholar] [CrossRef] [PubMed]
- Pinto, N.R.; Applebaum, M.A.; Volchenboum, S.L.; Matthay, K.K.; London, W.B.; Ambros, P.F.; Nakagawara, A.; Berthold, F.; Schleiermacher, G.; Park, J.R.; et al. Advances in Risk Classification and Treatment Strategies for Neuroblastoma. J. Clin. Oncol. 2015, 33, 3008–3017. [Google Scholar] [CrossRef] [PubMed]
- Brahmer, J.R.; Tykodi, S.S.; Chow, L.Q.M.; Hwu, W.-J.; Topalian, S.L.; Hwu, P.; Drake, C.G.; Camacho, L.H.; Kauh, J.; Odunsi, K.; et al. Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer. N. Engl. J. Med. 2012, 366, 2455–2465. [Google Scholar] [CrossRef] [PubMed]
- Hodi, F.S.; O’Day, S.J.; McDermott, D.F.; Weber, R.W.; Sosman, J.A.; Haanen, J.B.; Gonzalez, R.; Robert, C.; Schadendorf, D.; Hassel, J.C.; et al. Improved Survival with Ipilimumab in Patients with Metastatic Melanoma. N. Engl. J. Med. 2010, 363, 711–723. [Google Scholar] [CrossRef] [PubMed]
- Merchant, M.S.; Wright, M.; Baird, K.; Wexler, L.H.; Rodriguez-Galindo, C.; Bernstein, D.; Delbrook, C.; Lodish, M.; Bishop, R.; Wolchok, J.D.; et al. Phase I Clinical Trial of Ipilimumab in Pediatric Patients with Advanced Solid Tumors. Clin. Cancer Res. 2016, 22, 1364–1370. [Google Scholar] [CrossRef]
- Joshi, S. Targeting the Tumor Microenvironment in Neuroblastoma: Recent Advances and Future Directions. Cancers 2020, 12, 2057. [Google Scholar] [CrossRef]
- Gröbner, S.N.; Worst, B.C.; Weischenfeldt, J.; Buchhalter, I.; Kleinheinz, K.; Rudneva, V.A.; Johann, P.D.; Balasubramanian, G.P.; Segura-Wang, M.; Brabetz, S.; et al. The landscape of genomic alterations across childhood cancers. Nature 2018, 555, 321–327. [Google Scholar] [CrossRef]
- Prigione, I.; Corrias, M.V.; Airoldi, I.; Raffaghello, L.; Morandi, F.; Bocca, P.; Cocco, C.; Ferrone, S.; Pistoia, V. Immunogenicity of human neuroblastoma. Ann. N. Y. Acad. Sci. 2004, 1028, 69–80. [Google Scholar] [CrossRef]
- Wölfl, M.; Jungbluth, A.A.; Garrido, F.; Cabrera, T.; Meyen-Southard, S.; Spitz, R.; Ernestus, K.; Berthold, F. Expression of MHC class I, MHC class II, and cancer germline antigens in neuroblastoma. Cancer Immunol. Immunother. 2005, 54, 400–406. [Google Scholar] [CrossRef] [PubMed]
- Raffaghello, L.; Prigione, I.; Airoldi, I.; Camoriano, M.; Morandi, F.; Bocca, P.; Gambini, C.; Ferrone, S.; Pistoia, V. Mechanisms of immune evasion of human neuroblastoma. Cancer Lett. 2005, 228, 155–161. [Google Scholar] [CrossRef]
- Asgharzadeh, S.; Salo, J.A.; Ji, L.; Oberthuer, A.; Fischer, M.; Berthold, F.; Hadjidaniel, M.; Liu, C.W.; Metelitsa, L.S.; Pique-Regi, R.; et al. Clinical significance of tumor-associated inflammatory cells in metastatic neuroblastoma. J. Clin. Oncol. 2012, 30, 3525–3532. [Google Scholar] [CrossRef]
- Frosch, J.; Leontari, I.; Anderson, J. Combined Effects of Myeloid Cells in the Neuroblastoma Tumor Microenvironment. Cancers 2021, 13, 1743. [Google Scholar] [CrossRef] [PubMed]
- Iolascon, A.; Giordani, L.; Borriello, A.; Carbone, R.; Izzo, A.; Tonini, G.P.; Gambini, C.; Della Ragione, F. Reduced expression of transforming growth factor-beta receptor type III in high stage neuroblastomas. Br. J. Cancer 2000, 82, 1171–1176. [Google Scholar] [CrossRef] [PubMed]
- Bergenfelz, C.; Leandersson, K. The Generation and Identity of Human Myeloid-Derived Suppressor Cells. Front. Oncol. 2020, 10, 109. [Google Scholar] [CrossRef]
- Bronte, V.; Brandau, S.; Chen, S.H.; Colombo, M.P.; Frey, A.B.; Greten, T.F.; Mandruzzato, S.; Murray, P.J.; Ochoa, A.; Ostrand-Rosenberg, S.; et al. Recommendations for myeloid-derived suppressor cell nomenclature and characterization standards. Nat. Commun. 2016, 7, 12150. [Google Scholar] [CrossRef]
- Franklin, R.A.; Liao, W.; Sarkar, A.; Kim, M.V.; Bivona, M.R.; Liu, K.; Pamer, E.G.; Li, M.O. The cellular and molecular origin of tumor-associated macrophages. Science 2014, 344, 921–925. [Google Scholar] [CrossRef]
- Yang, L.; Zhang, Y. Tumor-associated macrophages: From basic research to clinical application. J. Hematol. Oncol. 2017, 10, 58. [Google Scholar] [CrossRef] [PubMed]
- Hadjidaniel, M.D.; Muthugounder, S.; Hung, L.T.; Sheard, M.A.; Shirinbak, S.; Chan, R.Y.; Nakata, R.; Borriello, L.; Malvar, J.; Kennedy, R.J.; et al. Tumor-associated macrophages promote neuroblastoma via STAT3 phosphorylation and up-regulation of c-MYC. Oncotarget 2017, 8, 91516–91529. [Google Scholar] [CrossRef] [PubMed]
- Pietras, A.; Gisselsson, D.; Ora, I.; Noguera, R.; Beckman, S.; Navarro, S.; Påhlman, S. High levels of HIF-2alpha highlight an immature neural crest-like neuroblastoma cell cohort located in a perivascular niche. J. Pathol. 2008, 214, 482–488. [Google Scholar] [CrossRef] [PubMed]
- Ribatti, D.; Vacca, A.; Nico, B.; De Falco, G.; Giuseppe Montaldo, P.; Ponzoni, M. Angiogenesis and anti-angiogenesis in neuroblastoma. Eur. J. Cancer 2002, 38, 750–757. [Google Scholar] [CrossRef] [PubMed]
- Hashimoto, O.; Yoshida, M.; Koma, Y.; Yanai, T.; Hasegawa, D.; Kosaka, Y.; Nishimura, N.; Yokozaki, H. Collaboration of cancer-associated fibroblasts and tumour-associated macrophages for neuroblastoma development. J. Pathol. 2016, 240, 211–223. [Google Scholar] [CrossRef] [PubMed]
- Liu, K.X.; Joshi, S. “Re-educating” Tumor Associated Macrophages as a Novel Immunotherapy Strategy for Neuroblastoma. Front. Immunol. 2020, 11, 1947. [Google Scholar] [CrossRef] [PubMed]
- Shirinbak, S.; Chan, R.Y.; Shahani, S.; Muthugounder, S.; Kennedy, R.; Hung, L.T.; Fernandez, G.E.; Hadjidaniel, M.D.; Moghimi, B.; Sheard, M.A.; et al. Combined immune checkpoint blockade increases CD8+CD28+PD-1+ effector T cells and provides a therapeutic strategy for patients with neuroblastoma. Oncoimmunology 2021, 10, 1838140. [Google Scholar] [CrossRef]
- Xu, Y.; Sun, J.; Sheard, M.A.; Tran, H.C.; Wan, Z.; Liu, W.Y.; Asgharzadeh, S.; Sposto, R.; Wu, H.W.; Seeger, R.C. Lenalidomide overcomes suppression of human natural killer cell anti-tumor functions by neuroblastoma microenvironment-associated IL-6 and TGFβ1. Cancer Immunol. Immunother. 2013, 62, 1637–1648. [Google Scholar] [CrossRef] [PubMed]
- Lanza, C.; Morando, S.; Voci, A.; Canesi, L.; Principato, M.C.; Serpero, L.D.; Mancardi, G.; Uccelli, A.; Vergani, L. Neuroprotective mesenchymal stem cells are endowed with a potent antioxidant effect in vivo. J. Neurochem. 2009, 110, 1674–1684. [Google Scholar] [CrossRef]
- Kumar, V.; Patel, S.; Tcyganov, E.; Gabrilovich, D.I. The Nature of Myeloid-Derived Suppressor Cells in the Tumor Microenvironment. Trends Immunol. 2016, 37, 208–220. [Google Scholar] [CrossRef]
- Santilli, G.; Piotrowska, I.; Cantilena, S.; Chayka, O.; D’Alicarnasso, M.; Morgenstern, D.A.; Himoudi, N.; Pearson, K.; Anderson, J.; Thrasher, A.J.; et al. Polyphenon [corrected] E enhances the antitumor immune response in neuroblastoma by inactivating myeloid suppressor cells. Clin. Cancer Res. 2013, 19, 1116–1125. [Google Scholar] [CrossRef] [PubMed]
- Lang, S.; Bruderek, K.; Kaspar, C.; Höing, B.; Kanaan, O.; Dominas, N.; Hussain, T.; Droege, F.; Eyth, C.; Hadaschik, B.; et al. Clinical Relevance and Suppressive Capacity of Human Myeloid-Derived Suppressor Cell Subsets. Clin. Cancer Res. 2018, 24, 4834–4844. [Google Scholar] [CrossRef] [PubMed]
- Gabrilovich, D.I.; Bronte, V.; Chen, S.H.; Colombo, M.P.; Ochoa, A.; Ostrand-Rosenberg, S.; Schreiber, H. The terminology issue for myeloid-derived suppressor cells. Cancer Res. 2007, 67, 425. [Google Scholar] [CrossRef] [PubMed]
- Youn, J.I.; Nagaraj, S.; Collazo, M.; Gabrilovich, D.I. Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J. Immunol. 2008, 181, 5791–5802. [Google Scholar] [CrossRef] [PubMed]
- Liao, Y.M.; Hung, T.H.; Tung, J.K.; Yu, J.; Hsu, Y.L.; Hung, J.T.; Yu, A.L. Low Expression of IL-15 and NKT in Tumor Microenvironment Predicts Poor Outcome of MYCN-Non-Amplified Neuroblastoma. J. Pers. Med. 2021, 11, 122. [Google Scholar] [CrossRef] [PubMed]
- Neviani, P.; Wise, P.M.; Murtadha, M.; Liu, C.W.; Wu, C.H.; Jong, A.Y.; Seeger, R.C.; Fabbri, M. Natural Killer-Derived Exosomal miR-186 Inhibits Neuroblastoma Growth and Immune Escape Mechanisms. Cancer Res. 2019, 79, 1151–1164. [Google Scholar] [CrossRef] [PubMed]
- Lode, H.N.; Xiang, R.; Dreier, T.; Varki, N.M.; Gillies, S.D.; Reisfeld, R.A. Natural killer cell-mediated eradication of neuroblastoma metastases to bone marrow by targeted interleukin-2 therapy. Blood 1998, 91, 1706–1715. [Google Scholar] [CrossRef]
- Martin, R.F.; Beckwith, J.B. Lymphoid infiltrates in neuroblastomas: Their occurrence and prognostic significance. J. Pediatr. Surg. 1968, 3, 161–164. [Google Scholar] [CrossRef]
- Wienke, J.; Dierselhuis, M.P.; Tytgat, G.A.M.; Künkele, A.; Nierkens, S.; Molenaar, J.J. The immune landscape of neuroblastoma: Challenges and opportunities for novel therapeutic strategies in pediatric oncology. Eur. J. Cancer 2021, 144, 123–150. [Google Scholar] [CrossRef]
- Coughlin, C.M.; Fleming, M.D.; Carroll, R.G.; Pawel, B.R.; Hogarty, M.D.; Shan, X.; Vance, B.A.; Cohen, J.N.; Jairaj, S.; Lord, E.M.; et al. Immunosurveillance and survivin-specific T-cell immunity in children with high-risk neuroblastoma. J. Clin. Oncol. 2006, 24, 5725–5734. [Google Scholar] [CrossRef]
- Asgharzadeh, S.; Pique-Regi, R.; Sposto, R.; Wang, H.; Yang, Y.; Shimada, H.; Matthay, K.; Buckley, J.; Ortega, A.; Seeger, R.C. Prognostic significance of gene expression profiles of metastatic neuroblastomas lacking MYCN gene amplification. J. Natl. Cancer Inst. 2006, 98, 1193–1203. [Google Scholar] [CrossRef]
- Soldati, R.; Berger, E.; Zenclussen, A.C.; Jorch, G.; Lode, H.N.; Salatino, M.; Rabinovich, G.A.; Fest, S. Neuroblastoma triggers an immunoevasive program involving galectin-1-dependent modulation of T cell and dendritic cell compartments. Int. J. Cancer 2012, 131, 1131–1141. [Google Scholar] [CrossRef]
- Song, L.; Asgharzadeh, S.; Salo, J.; Engell, K.; Wu, H.W.; Sposto, R.; Ara, T.; Silverman, A.M.; DeClerck, Y.A.; Seeger, R.C.; et al. Valpha24-invariant NKT cells mediate antitumor activity via killing of tumor-associated macrophages. J. Clin. Investig. 2009, 119, 1524–1536. [Google Scholar] [CrossRef]
- Vanichapol, T.; Chutipongtanate, S.; Anurathapan, U.; Hongeng, S. Immune Escape Mechanisms and Future Prospects for Immunotherapy in Neuroblastoma. Biomed Res. Int. 2018, 2018, 1812535. [Google Scholar] [CrossRef]
- Facchetti, P.; Prigione, I.; Ghiotto, F.; Tasso, P.; Garaventa, A.; Pistoia, V. Functional and molecular characterization of tumour-infiltrating lymphocytes and clones thereof from a major-histocompatibility-complex-negative human tumour: Neuroblastoma. Cancer Immunol. Immunother. 1996, 42, 170–178. [Google Scholar] [CrossRef] [PubMed]
- Blavier, L.; Yang, R.M.; DeClerck, Y.A. The Tumor Microenvironment in Neuroblastoma: New Players, New Mechanisms of Interaction and New Perspectives. Cancers 2020, 12, 2912. [Google Scholar] [CrossRef]
- Ohue, Y.; Nishikawa, H. Regulatory T (Treg) cells in cancer: Can Treg cells be a new therapeutic target? Cancer Sci. 2019, 110, 2080–2089. [Google Scholar] [CrossRef]
- Zou, W. Regulatory T cells, tumour immunity and immunotherapy. Nat. Rev. Immunol. 2006, 6, 295–307. [Google Scholar] [CrossRef] [PubMed]
- Gattinoni, L.; Finkelstein, S.E.; Klebanoff, C.A.; Antony, P.A.; Palmer, D.C.; Spiess, P.J.; Hwang, L.N.; Yu, Z.; Wrzesinski, C.; Heimann, D.M.; et al. Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8+ T cells. J. Exp. Med. 2005, 202, 907–912. [Google Scholar] [CrossRef] [PubMed]
- Kerkar, S.P.; Restifo, N.P. Cellular constituents of immune escape within the tumor microenvironment. Cancer Res. 2012, 72, 3125–3130. [Google Scholar] [CrossRef]
- Matsui, S.; Ahlers, J.D.; Vortmeyer, A.O.; Terabe, M.; Tsukui, T.; Carbone, D.P.; Liotta, L.A.; Berzofsky, J.A. A model for CD8+ CTL tumor immunosurveillance and regulation of tumor escape by CD4 T cells through an effect on quality of CTL. J. Immunol. 1999, 163, 184–193. [Google Scholar] [CrossRef]
- Johnson, B.D.; Jing, W.; Orentas, R.J. CD25+ regulatory T cell inhibition enhances vaccine-induced immunity to neuroblastoma. J. Immunother. 2007, 30, 203–214. [Google Scholar] [CrossRef]
- Rigo, V.; Corrias, M.V.; Orengo, A.M.; Brizzolara, A.; Emionite, L.; Fenoglio, D.; Filaci, G.; Croce, M.; Ferrini, S. Recombinant IL-21 and anti-CD4 antibodies cooperate in syngeneic neuroblastoma immunotherapy and mediate long-lasting immunity. Cancer Immunol. Immunother. 2014, 63, 501–511. [Google Scholar] [CrossRef]
- Sun, J.; Dotti, G.; Huye, L.E.; Foster, A.E.; Savoldo, B.; Gramatges, M.M.; Spencer, D.M.; Rooney, C.M. T cells expressing constitutively active Akt resist multiple tumor-associated inhibitory mechanisms. Mol. Ther. 2010, 18, 2006–2017. [Google Scholar] [CrossRef] [PubMed]
- Richards, R.M.; Sotillo, E.; Majzner, R.G. CAR T Cell Therapy for Neuroblastoma. Front. Immunol. 2018, 9, 2380. [Google Scholar] [CrossRef]
- De Veirman, K.; Rao, L.; De Bruyne, E.; Menu, E.; Van Valckenborgh, E.; Van Riet, I.; Frassanito, M.A.; Di Marzo, L.; Vacca, A.; Vanderkerken, K. Cancer associated fibroblasts and tumor growth: Focus on multiple myeloma. Cancers 2014, 6, 1363–1381. [Google Scholar] [CrossRef] [PubMed]
- Tran, H.C.; Wan, Z.; Sheard, M.A.; Sun, J.; Jackson, J.R.; Malvar, J.; Xu, Y.; Wang, L.; Sposto, R.; Kim, E.S.; et al. TGFβR1 Blockade with Galunisertib (LY2157299) Enhances Anti-Neuroblastoma Activity of the Anti-GD2 Antibody Dinutuximab (ch14.18) with Natural Killer Cells. Clin. Cancer Res. 2017, 23, 804–813. [Google Scholar] [CrossRef] [PubMed]
- Zeine, R.; Salwen, H.R.; Peddinti, R.; Tian, Y.; Guerrero, L.; Yang, Q.; Chlenski, A.; Cohn, S.L. Presence of cancer-associated fibroblasts inversely correlates with Schwannian stroma in neuroblastoma tumors. Mod. Pathol. 2009, 22, 950–958. [Google Scholar] [CrossRef]
- Kock, A.; Larsson, K.; Bergqvist, F.; Eissler, N.; Elfman, L.H.M.; Raouf, J.; Korotkova, M.; Johnsen, J.I.; Jakobsson, P.J.; Kogner, P. Inhibition of Microsomal Prostaglandin E Synthase-1 in Cancer-Associated Fibroblasts Suppresses Neuroblastoma Tumor Growth. EBioMedicine 2018, 32, 84–92. [Google Scholar] [CrossRef] [PubMed]
- Silzle, T.; Kreutz, M.; Dobler, M.A.; Brockhoff, G.; Knuechel, R.; Kunz-Schughart, L.A. Tumor-associated fibroblasts recruit blood monocytes into tumor tissue. Eur. J. Immunol. 2003, 33, 1311–1320. [Google Scholar] [CrossRef]
- Pelizzo, G.; Veschi, V.; Mantelli, M.; Croce, S.; Di Benedetto, V.; D’Angelo, P.; Maltese, A.; Catenacci, L.; Apuzzo, T.; Scavo, E.; et al. Microenvironment in neuroblastoma: Isolation and characterization of tumor-derived mesenchymal stromal cells. BMC Cancer 2018, 18, 1176. [Google Scholar] [CrossRef] [PubMed]
- Sugiura, Y.; Shimada, H.; Seeger, R.C.; Laug, W.E.; DeClerck, Y.A. Matrix metalloproteinases-2 and -9 are expressed in human neuroblastoma: Contribution of stromal cells to their production and correlation with metastasis. Cancer Res. 1998, 58, 2209–2216. [Google Scholar]
- Ma, M.; Ye, J.Y.; Deng, R.; Dee, C.M.; Chan, G.C. Mesenchymal stromal cells may enhance metastasis of neuroblastoma via SDF-1/CXCR4 and SDF-1/CXCR7 signaling. Cancer Lett. 2011, 312, 1–10. [Google Scholar] [CrossRef]
- Airoldi, I.; Cocco, C.; Morandi, F.; Prigione, I.; Pistoia, V. CXCR5 may be involved in the attraction of human metastatic neuroblastoma cells to the bone marrow. Cancer Immunol. Immunother. 2008, 57, 541–548. [Google Scholar] [CrossRef] [PubMed]
- Hochheuser, C.; Windt, L.J.; Kunze, N.Y.; de Vos, D.L.; Tytgat, G.A.M.; Voermans, C.; Timmerman, I. Mesenchymal Stromal Cells in Neuroblastoma: Exploring Crosstalk and Therapeutic Implications. Stem Cells Dev. 2021, 30, 59–78. [Google Scholar] [CrossRef]
- Wu, H.W.; Sheard, M.A.; Malvar, J.; Fernandez, G.E.; DeClerck, Y.A.; Blavier, L.; Shimada, H.; Theuer, C.P.; Sposto, R.; Seeger, R.C. Anti-CD105 Antibody Eliminates Tumor Microenvironment Cells and Enhances Anti-GD2 Antibody Immunotherapy of Neuroblastoma with Activated Natural Killer Cells. Clin. Cancer Res. 2019, 25, 4761–4774. [Google Scholar] [CrossRef]
- Dong, R.; Yang, R.; Zhan, Y.; Lai, H.D.; Ye, C.J.; Yao, X.Y.; Luo, W.Q.; Cheng, X.M.; Miao, J.J.; Wang, J.F.; et al. Single-Cell Characterization of Malignant Phenotypes and Developmental Trajectories of Adrenal Neuroblastoma. Cancer Cell 2020, 38, 716–733.e6. [Google Scholar] [CrossRef] [PubMed]
- Kwiatkowski, J.L.; Rutkowski, J.L.; Yamashiro, D.J.; Tennekoon, G.I.; Brodeur, G.M. Schwann cell-conditioned medium promotes neuroblastoma survival and differentiation. Cancer Res. 1998, 58, 4602–4606. [Google Scholar] [PubMed]
- Pajtler, K.W.; Mahlow, E.; Odersky, A.; Lindner, S.; Stephan, H.; Bendix, I.; Eggert, A.; Schramm, A.; Schulte, J.H. Neuroblastoma in dialog with its stroma: NTRK1 is a regulator of cellular cross-talk with Schwann cells. Oncotarget 2014, 5, 11180–11192. [Google Scholar] [CrossRef]
- Weiss, T.; Taschner-Mandl, S.; Janker, L.; Bileck, A.; Rifatbegovic, F.; Kromp, F.; Sorger, H.; Kauer, M.O.; Frech, C.; Windhager, R.; et al. Schwann cell plasticity regulates neuroblastic tumor cell differentiation via epidermal growth factor-like protein 8. Nat. Commun. 2021, 12, 1624. [Google Scholar] [CrossRef]
- Liu, Y.; Song, L. HMGB1-induced autophagy in Schwann cells promotes neuroblastoma proliferation. Int. J. Clin. Exp. Pathol. 2015, 8, 504–510. [Google Scholar]
- Kleinman, N.R.; Lewandowska, K.; Culp, L.A. Tumour progression of human neuroblastoma cells tagged with a lacZ marker gene: Earliest events at ectopic injection sites. Br. J. Cancer 1994, 69, 670–679. [Google Scholar] [CrossRef] [PubMed]
- Meister, B.; Grünebach, F.; Bautz, F.; Brugger, W.; Fink, F.M.; Kanz, L.; Möhle, R. Expression of vascular endothelial growth factor (VEGF) and its receptors in human neuroblastoma. Eur. J. Cancer 1999, 35, 445–449. [Google Scholar] [CrossRef]
- Meitar, D.; Crawford, S.E.; Rademaker, A.W.; Cohn, S.L. Tumor angiogenesis correlates with metastatic disease, N-myc amplification, and poor outcome in human neuroblastoma. J. Clin. Oncol. 1996, 14, 405–414. [Google Scholar] [CrossRef] [PubMed]
- Dickson, P.V.; Hamner, J.B.; Sims, T.L.; Fraga, C.H.; Ng, C.Y.; Rajasekeran, S.; Hagedorn, N.L.; McCarville, M.B.; Stewart, C.F.; Davidoff, A.M. Bevacizumab-induced transient remodeling of the vasculature in neuroblastoma xenografts results in improved delivery and efficacy of systemically administered chemotherapy. Clin. Cancer Res. 2007, 13, 3942–3950. [Google Scholar] [CrossRef]
- Hagendoorn, J.; Tong, R.; Fukumura, D.; Lin, Q.; Lobo, J.; Padera, T.P.; Xu, L.; Kucherlapati, R.; Jain, R.K. Onset of abnormal blood and lymphatic vessel function and interstitial hypertension in early stages of carcinogenesis. Cancer Res. 2006, 66, 3360–3364. [Google Scholar] [CrossRef]
- Corrias, M.V.; Occhino, M.; Croce, M.; De Ambrosis, A.; Pistillo, M.P.; Bocca, P.; Pistoia, V.; Ferrini, S. Lack of HLA-class I antigens in human neuroblastoma cells: Analysis of its relationship to TAP and tapasin expression. Tissue Antigens 2001, 57, 110–117. [Google Scholar] [CrossRef]
- Shurin, G.V.; Gerein, V.; Lotze, M.T.; Barksdale, E.M., Jr. Apoptosis induced in T cells by human neuroblastoma cells: Role of Fas ligand. Nat. Immun. 1998, 16, 263–274. [Google Scholar] [CrossRef]
- Brandetti, E.; Veneziani, I.; Melaiu, O.; Pezzolo, A.; Castellano, A.; Boldrini, R.; Ferretti, E.; Fruci, D.; Moretta, L.; Pistoia, V.; et al. MYCN is an immunosuppressive oncogene dampening the expression of ligands for NK-cell-activating receptors in human high-risk neuroblastoma. Oncoimmunology 2017, 6, e1316439. [Google Scholar] [CrossRef]
- Raffaghello, L.; Prigione, I.; Airoldi, I.; Camoriano, M.; Levreri, I.; Gambini, C.; Pende, D.; Steinle, A.; Ferrone, S.; Pistoia, V. Downregulation and/or release of NKG2D ligands as immune evasion strategy of human neuroblastoma. Neoplasia 2004, 6, 558–568. [Google Scholar] [CrossRef] [PubMed]
- Zhang, P.; Wu, X.; Basu, M.; Dong, C.; Zheng, P.; Liu, Y.; Sandler, A.D. MYCN Amplification Is Associated with Repressed Cellular Immunity in Neuroblastoma: An In Silico Immunological Analysis of TARGET Database. Front. Immunol. 2017, 8, 1473. [Google Scholar] [CrossRef] [PubMed]
- Rodriguez, P.C.; Quiceno, D.G.; Ochoa, A.C. L-arginine availability regulates T-lymphocyte cell-cycle progression. Blood 2007, 109, 1568–1573. [Google Scholar] [CrossRef] [PubMed]
- Vanichapol, T.; Chiangjong, W.; Panachan, J.; Anurathapan, U.; Chutipongtanate, S.; Hongeng, S. Secretory High-Mobility Group Box 1 Protein Affects Regulatory T Cell Differentiation in Neuroblastoma Microenvironment In Vitro. J. Oncol. 2018, 2018, 7946021. [Google Scholar] [CrossRef]
- Chlenski, A.; Liu, S.; Guerrero, L.J.; Yang, Q.; Tian, Y.; Salwen, H.R.; Zage, P.; Cohn, S.L. SPARC expression is associated with impaired tumor growth, inhibited angiogenesis and changes in the extracellular matrix. Int. J. Cancer 2006, 118, 310–316. [Google Scholar] [CrossRef] [PubMed]
- Yan, X.; Orentas, R.J.; Johnson, B.D. Tumor-derived macrophage migration inhibitory factor (MIF) inhibits T lymphocyte activation. Cytokine 2006, 33, 188–198. [Google Scholar] [CrossRef] [PubMed]
- Brown, C.E.; Vishwanath, R.P.; Aguilar, B.; Starr, R.; Najbauer, J.; Aboody, K.S.; Jensen, M.C. Tumor-derived chemokine MCP-1/CCL2 is sufficient for mediating tumor tropism of adoptively transferred T cells. J. Immunol. 2007, 179, 3332–3341. [Google Scholar] [CrossRef] [PubMed]
- Esaki, N.; Ohkawa, Y.; Hashimoto, N.; Tsuda, Y.; Ohmi, Y.; Bhuiyan, R.H.; Kotani, N.; Honke, K.; Enomoto, A.; Takahashi, M.; et al. ASC amino acid transporter 2, defined by enzyme-mediated activation of radical sources, enhances malignancy of GD2-positive small-cell lung cancer. Cancer Sci. 2018, 109, 141–153. [Google Scholar] [CrossRef] [PubMed]
- Nazha, B.; Inal, C.; Owonikoko, T.K. Disialoganglioside GD2 Expression in Solid Tumors and Role as a Target for Cancer Therapy. Front. Oncol. 2020, 10, 1000. [Google Scholar] [CrossRef]
- Wu, Z.L.; Schwartz, E.; Seeger, R.; Ladisch, S. Expression of GD2 ganglioside by untreated primary human neuroblastomas. Cancer Res. 1986, 46, 440–443. [Google Scholar]
- Yoshida, S.; Fukumoto, S.; Kawaguchi, H.; Sato, S.; Ueda, R.; Furukawa, K. Ganglioside G(D2) in small cell lung cancer cell lines: Enhancement of cell proliferation and mediation of apoptosis. Cancer Res. 2001, 61, 4244–4252. [Google Scholar]
- Dhillon, S. Dinutuximab: First global approval. Drugs 2015, 75, 923–927. [Google Scholar] [CrossRef]
- Yu, A.L.; Gilman, A.L.; Ozkaynak, M.F.; Naranjo, A.; Diccianni, M.B.; Gan, J.; Hank, J.A.; Batova, A.; London, W.B.; Tenney, S.C.; et al. Long-Term Follow-up of a Phase III Study of ch14.18 (Dinutuximab) + Cytokine Immunotherapy in Children with High-Risk Neuroblastoma: COG Study ANBL0032. Clin. Cancer Res. 2021, 27, 2179–2189. [Google Scholar] [CrossRef] [PubMed]
- Furman, W.L.; Federico, S.M.; McCarville, M.B.; Shulkin, B.L.; Davidoff, A.M.; Krasin, M.J.; Sahr, N.; Sykes, A.; Wu, J.; Brennan, R.C.; et al. A Phase II Trial of Hu14.18K322A in Combination with Induction Chemotherapy in Children with Newly Diagnosed High-Risk Neuroblastoma. Clin. Cancer Res. 2019, 25, 6320–6328. [Google Scholar] [CrossRef] [PubMed]
- Furman, W.L.; McCarville, B.; Shulkin, B.L.; Davidoff, A.; Krasin, M.; Hsu, C.W.; Pan, H.; Wu, J.; Brennan, R.; Bishop, M.W.; et al. Improved Outcome in Children With Newly Diagnosed High-Risk Neuroblastoma Treated With Chemoimmunotherapy: Updated Results of a Phase II Study Using hu14.18K322A. J. Clin. Oncol. 2022, 40, 335–344. [Google Scholar] [CrossRef]
- Ladenstein, R.; Pötschger, U.; Valteau-Couanet, D.; Luksch, R.; Castel, V.; Yaniv, I.; Laureys, G.; Brock, P.; Michon, J.M.; Owens, C.; et al. Interleukin 2 with anti-GD2 antibody ch14.18/CHO (dinutuximab beta) in patients with high-risk neuroblastoma (HR-NBL1/SIOPEN): A multicentre, randomised, phase 3 trial. Lancet Oncol. 2018, 19, 1617–1629. [Google Scholar] [CrossRef]
- Mora, J.; Modak, S.; Kinsey, J.; Ragsdale, C.E.; Lazarus, H.M. GM-CSF, G-CSF or no cytokine therapy with anti-GD2 immunotherapy for high-risk neuroblastoma. Int. J. Cancer 2024, 154, 1340–1364. [Google Scholar] [CrossRef]
- Yu, A.L.; Gilman, A.L.; Ozkaynak, M.F.; London, W.B.; Kreissman, S.G.; Chen, H.X.; Smith, M.; Anderson, B.; Villablanca, J.G.; Matthay, K.K.; et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. N. Engl. J. Med. 2010, 363, 1324–1334. [Google Scholar] [CrossRef] [PubMed]
- Loo, D.; Alderson, R.F.; Chen, F.Z.; Huang, L.; Zhang, W.; Gorlatov, S.; Burke, S.; Ciccarone, V.; Li, H.; Yang, Y.; et al. Development of an Fc-enhanced anti-B7-H3 monoclonal antibody with potent antitumor activity. Clin. Cancer Res. 2012, 18, 3834–3845. [Google Scholar] [CrossRef]
- Majzner, R.G.; Theruvath, J.L.; Nellan, A.; Heitzeneder, S.; Cui, Y.; Mount, C.W.; Rietberg, S.P.; Linde, M.H.; Xu, P.; Rota, C.; et al. CAR T cells targeting B7-H3, a Pan-cancer antigen, demonstrate potent preclinical activity against pediatric solid tumors and brain Tumors. Clin. Cancer Res. 2019, 25, 2560–2574. [Google Scholar] [CrossRef]
- Rosenkrans, Z.T.; Erbe, A.K.; Clemons, N.B.; Feils, A.S.; Medina-Guevara, Y.; Jeffery, J.J.; Barnhart, T.E.; Engle, J.W.; Sondel, P.M.; Hernandez, R. Targeting both GD2 and B7-H3 using bispecific antibody improves tumor selectivity for GD2-positive tumors. bioRxiv 2024, arXiv:2024.05.23.595624. [Google Scholar]
- Caescu, C.I.; Guo, X.; Tesfa, L.; Bhagat, T.D.; Verma, A.; Zheng, D.; Stanley, E.R. Colony stimulating factor-1 receptor signaling networks inhibit mouse macrophage inflammatory responses by induction of microRNA-21. Blood 2015, 125, e1–e13. [Google Scholar] [CrossRef] [PubMed]
- Mao, Y.; Eissler, N.; Blanc, K.L.; Johnsen, J.I.; Kogner, P.; Kiessling, R. Targeting Suppressive Myeloid Cells Potentiates Checkpoint Inhibitors to Control Spontaneous Neuroblastoma. Clin. Cancer Res. 2016, 22, 3849–3859. [Google Scholar] [CrossRef] [PubMed]
- Webb, M.W.; Sun, J.; Sheard, M.A.; Liu, W.Y.; Wu, H.W.; Jackson, J.R.; Malvar, J.; Sposto, R.; Daniel, D.; Seeger, R.C. Colony stimulating factor 1 receptor blockade improves the efficacy of chemotherapy against human neuroblastoma in the absence of T lymphocytes. Int. J. Cancer 2018, 143, 1483–1493. [Google Scholar] [CrossRef] [PubMed]
- Carlson, L.M.; Rasmuson, A.; Idborg, H.; Segerström, L.; Jakobsson, P.J.; Sveinbjörnsson, B.; Kogner, P. Low-dose aspirin delays an inflammatory tumor progression in vivo in a transgenic mouse model of neuroblastoma. Carcinogenesis 2013, 34, 1081–1088. [Google Scholar] [CrossRef] [PubMed]
- Siebert, N.; Zumpe, M.; von Lojewski, L.; Troschke-Meurer, S.; Marx, M.; Lode, H.N. Reduction of CD11b(+) myeloid suppressive cells augments anti-neuroblastoma immune response induced by the anti-GD(2) antibody ch14.18/CHO. Oncoimmunology 2020, 9, 1836768. [Google Scholar] [CrossRef] [PubMed]
- Dierckx de Casterlé, I.; Fevery, S.; Rutgeerts, O.; Poosti, F.; Struyf, S.; Lenaerts, C.; Waer, M.; Billiau, A.D.; Sprangers, B. Reduction of myeloid-derived suppressor cells reinforces the anti-solid tumor effect of recipient leukocyte infusion in murine neuroblastoma-bearing allogeneic bone marrow chimeras. Cancer Immunol. Immunother. 2018, 67, 589–603. [Google Scholar] [CrossRef] [PubMed]
- Parihar, R.; Rivas, C.; Huynh, M.; Omer, B.; Lapteva, N.; Metelitsa, L.S.; Gottschalk, S.M.; Rooney, C.M. NK Cells Expressing a Chimeric Activating Receptor Eliminate MDSCs and Rescue Impaired CAR-T Cell Activity against Solid Tumors. Cancer Immunol. Res. 2019, 7, 363–375. [Google Scholar] [CrossRef] [PubMed]
- Kroesen, M.; Büll, C.; Gielen, P.R.; Brok, I.C.; Armandari, I.; Wassink, M.; Looman, M.W.; Boon, L.; den Brok, M.H.; Hoogerbrugge, P.M.; et al. Anti-GD2 mAb and Vorinostat synergize in the treatment of neuroblastoma. Oncoimmunology 2016, 5, e1164919. [Google Scholar] [CrossRef] [PubMed]
- Redlinger, R.E., Jr.; Mailliard, R.B.; Lotze, M.T.; Barksdale, E.M., Jr. Synergistic interleukin-18 and low-dose interleukin-2 promote regression of established murine neuroblastoma in vivo. J. Pediatr. Surg. 2003, 38, 301–307. [Google Scholar] [CrossRef]
- Zeng, Y.; Huebener, N.; Fest, S.; Weixler, S.; Schroeder, U.; Gaedicke, G.; Xiang, R.; Schramm, A.; Eggert, A.; Reisfeld, R.A.; et al. Fractalkine (CX3CL1)- and interleukin-2-enriched neuroblastoma microenvironment induces eradication of metastases mediated by T cells and natural killer cells. Cancer Res. 2007, 67, 2331–2338. [Google Scholar] [CrossRef]
- Relation, T.; Yi, T.; Guess, A.J.; La Perle, K.; Otsuru, S.; Hasgur, S.; Dominici, M.; Breuer, C.; Horwitz, E.M. Intratumoral Delivery of Interferonγ-Secreting Mesenchymal Stromal Cells Repolarizes Tumor-Associated Macrophages and Suppresses Neuroblastoma Proliferation In Vivo. Stem Cells 2018, 36, 915–924. [Google Scholar] [CrossRef]
- Komorowski, M.; Tisonczyk, J.; Kolakowska, A.; Drozdz, R.; Kozbor, D. Modulation of the Tumor Microenvironment by CXCR4 Antagonist-Armed Viral Oncotherapy Enhances the Antitumor Efficacy of Dendritic Cell Vaccines against Neuroblastoma in Syngeneic Mice. Viruses 2018, 10, 455. [Google Scholar] [CrossRef] [PubMed]
- Shiravand, Y.; Khodadadi, F.; Kashani, S.M.A.; Hosseini-Fard, S.R.; Hosseini, S.; Sadeghirad, H.; Ladwa, R.; O’Byrne, K.; Kulasinghe, A. Immune Checkpoint Inhibitors in Cancer Therapy. Curr. Oncol. 2022, 29, 3044–3060. [Google Scholar] [CrossRef]
- Mora, J.; Modak, S. Nivolumab in paediatric cancer: Children are not little adults. Lancet Oncol. 2020, 21, 474–476. [Google Scholar] [CrossRef]
- Moreno-Vicente, J.; Willoughby, J.E.; Taylor, M.C.; Booth, S.G.; English, V.L.; Williams, E.L.; Penfold, C.A.; Mockridge, C.I.; Inzhelevskaya, T.; Kim, J.; et al. Fc-null anti-PD-1 monoclonal antibodies deliver optimal checkpoint blockade in diverse immune environments. J. Immunother. Cancer 2022, 10, e003735. [Google Scholar] [CrossRef] [PubMed]
- Srinivasan, P.; Wu, X.; Basu, M.; Rossi, C.; Sandler, A.D. PD-L1 checkpoint inhibition and anti-CTLA-4 whole tumor cell vaccination counter adaptive immune resistance: A mouse neuroblastoma model that mimics human disease. PLoS Med. 2018, 15, e1002497. [Google Scholar] [CrossRef]
- Melen, G.J.; Franco-Luzón, L.; Ruano, D.; González-Murillo, Á.; Alfranca, A.; Casco, F.; Lassaletta, Á.; Alonso, M.; Madero, L.; Alemany, R.; et al. Influence of carrier cells on the clinical outcome of children with neuroblastoma treated with high dose of oncolytic adenovirus delivered in mesenchymal stem cells. Cancer Lett. 2016, 371, 161–170. [Google Scholar] [CrossRef]
- Banerjee, D.; Hernandez, S.L.; Garcia, A.; Kangsamaksin, T.; Sbiroli, E.; Andrews, J.; Forrester, L.A.; Wei, N.; Kadenhe-Chiweshe, A.; Shawber, C.J.; et al. Notch suppresses angiogenesis and progression of hepatic metastases. Cancer Res. 2015, 75, 1592–1602. [Google Scholar] [CrossRef]
- Puppo, M.; Battaglia, F.; Ottaviano, C.; Delfino, S.; Ribatti, D.; Varesio, L.; Bosco, M.C. Topotecan inhibits vascular endothelial growth factor production and angiogenic activity induced by hypoxia in human neuroblastoma by targeting hypoxia-inducible factor-1α and -2α. Mol. Cancer Ther. 2008, 7, 1974–1984. [Google Scholar] [CrossRef]
- Baker, D.L.; Schmidt, M.L.; Cohn, S.L.; Maris, J.M.; London, W.B.; Buxton, A.; Stram, D.; Castleberry, R.P.; Shimada, H.; Sandler, A.; et al. Outcome after Reduced Chemotherapy for Intermediate-Risk Neuroblastoma. N. Engl. J. Med. 2010, 363, 1313–1323. [Google Scholar] [CrossRef] [PubMed]
- Gatta, G.; Botta, L.; Rossi, S.; Aareleid, T.; Bielska-Lasota, M.; Clavel, J.; Dimitrova, N.; Jakab, Z.; Kaatsch, P.; Lacour, B.; et al. Childhood cancer survival in Europe 1999–2007: Results of EUROCARE-5—A population-based study. Lancet Oncol. 2014, 15, 35–47. [Google Scholar] [CrossRef]
- Matthay, K.K.; Maris, J.M.; Schleiermacher, G.; Nakagawara, A.; Mackall, C.L.; Diller, L.; Weiss, W.A. Neuroblastoma. Nat. Rev. Dis. Primers 2016, 2, 16078. [Google Scholar] [CrossRef]
- Garaventa, A.; Parodi, S.; De Bernardi, B.; Dau, D.; Manzitti, C.; Conte, M.; Casale, F.; Viscardi, E.; Bianchi, M.; D’Angelo, P.; et al. Outcome of children with neuroblastoma after progression or relapse. A retrospective study of the Italian neuroblastoma registry. Eur. J. Cancer 2009, 45, 2835–2842. [Google Scholar] [CrossRef] [PubMed]
- Matthay, K.K.; Reynolds, C.P.; Seeger, R.C.; Shimada, H.; Adkins, E.S.; Haas-Kogan, D.; Gerbing, R.B.; London, W.B.; Villablanca, J.G. Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: A children’s oncology group study. J. Clin. Oncol. 2009, 27, 1007–1013. [Google Scholar] [CrossRef] [PubMed]
- Park, J.R.; Scott, J.R.; Stewart, C.F.; London, W.B.; Naranjo, A.; Santana, V.M.; Shaw, P.J.; Cohn, S.L.; Matthay, K.K. Pilot induction regimen incorporating pharmacokinetically guided topotecan for treatment of newly diagnosed high-risk neuroblastoma: A Children’s Oncology Group study. J. Clin. Oncol. 2011, 29, 4351–4357. [Google Scholar] [CrossRef]
- Hallberg, B.; Palmer, R.H. Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology. Nat. Rev. Cancer 2013, 13, 685–700. [Google Scholar] [CrossRef]
- Pearson, J.D.; Lee, J.K.; Bacani, J.T.; Lai, R.; Ingham, R.J. NPM-ALK: The Prototypic Member of a Family of Oncogenic Fusion Tyrosine Kinases. J. Signal Transduct. 2012, 2012, 123253. [Google Scholar] [CrossRef]
- Chiarle, R.; Voena, C.; Ambrogio, C.; Piva, R.; Inghirami, G. The anaplastic lymphoma kinase in the pathogenesis of cancer. Nat. Rev. Cancer 2008, 8, 11–23. [Google Scholar] [CrossRef] [PubMed]
- Passoni, L.; Longo, L.; Collini, P.; Coluccia, A.M.; Bozzi, F.; Podda, M.; Gregorio, A.; Gambini, C.; Garaventa, A.; Pistoia, V.; et al. Mutation-independent anaplastic lymphoma kinase overexpression in poor prognosis neuroblastoma patients. Cancer Res. 2009, 69, 7338–7346. [Google Scholar] [CrossRef]
- Schulte, J.H.; Bachmann, H.S.; Brockmeyer, B.; Depreter, K.; Oberthür, A.; Ackermann, S.; Kahlert, Y.; Pajtler, K.; Theissen, J.; Westermann, F.; et al. High ALK receptor tyrosine kinase expression supersedes ALK mutation as a determining factor of an unfavorable phenotype in primary neuroblastoma. Clin. Cancer Res. 2011, 17, 5082–5092. [Google Scholar] [CrossRef]
- Guo, Y.; Guo, H.; Zhang, Y.; Cui, J. Anaplastic lymphoma kinase-special immunity and immunotherapy. Front. Immunol. 2022, 13, 908894. [Google Scholar] [CrossRef]
- Eleveld, T.F.; Oldridge, D.A.; Bernard, V.; Koster, J.; Colmet Daage, L.; Diskin, S.J.; Schild, L.; Bentahar, N.B.; Bellini, A.; Chicard, M.; et al. Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations. Nat. Genet. 2015, 47, 864–871. [Google Scholar] [CrossRef]
- Mossé, Y.P.; Laudenslager, M.; Longo, L.; Cole, K.A.; Wood, A.; Attiyeh, E.F.; Laquaglia, M.J.; Sennett, R.; Lynch, J.E.; Perri, P.; et al. Identification of ALK as a major familial neuroblastoma predisposition gene. Nature 2008, 455, 930–935. [Google Scholar] [CrossRef]
- Schleiermacher, G.; Javanmardi, N.; Bernard, V.; Leroy, Q.; Cappo, J.; Rio Frio, T.; Pierron, G.; Lapouble, E.; Combaret, V.; Speleman, F.; et al. Emergence of new ALK mutations at relapse of neuroblastoma. J. Clin. Oncol. 2014, 32, 2727–2734. [Google Scholar] [CrossRef]
- Foster, J.H.; Voss, S.D.; Hall, D.C.; Minard, C.G.; Balis, F.M.; Wilner, K.; Berg, S.L.; Fox, E.; Adamson, P.C.; Blaney, S.M.; et al. Activity of Crizotinib in Patients with ALK-Aberrant Relapsed/Refractory Neuroblastoma: A Children’s Oncology Group Study (ADVL0912). Clin. Cancer Res. 2021, 27, 3543–3548. [Google Scholar] [CrossRef] [PubMed]
- Goldsmith, K.C.; Kayser, K.; Groshen, S.G.; Chioda, M.; Thurm, H.C.; Chen, J.; Peltz, G.; Granger, M.; Maris, J.; Matthay, K.K.; et al. Phase I trial of lorlatinib in patients with ALK-driven refractory or relapsed neuroblastoma: A New Approaches to Neuroblastoma Consortium study. J. Clin. Oncol. 2020, 38 (Suppl. S15), 10504. [Google Scholar] [CrossRef]
- Liu, T.; Merguerian, M.D.; Rowe, S.P.; Pratilas, C.A.; Chen, A.R.; Ladle, B.H. Exceptional response to the ALK and ROS1 inhibitor lorlatinib and subsequent mechanism of resistance in relapsed ALK F1174L-mutated neuroblastoma. Cold Spring Harb. Mol. Case Stud. 2021, 7, a006064. [Google Scholar] [CrossRef]
- Bresler, S.C.; Wood, A.C.; Haglund, E.A.; Courtright, J.; Belcastro, L.T.; Plegaria, J.S.; Cole, K.; Toporovskaya, Y.; Zhao, H.; Carpenter, E.L.; et al. Differential inhibitor sensitivity of anaplastic lymphoma kinase variants found in neuroblastoma. Sci. Transl. Med. 2011, 3, 108ra114. [Google Scholar] [CrossRef] [PubMed]
- Carpenter, E.L.; Mossé, Y.P. Targeting ALK in neuroblastoma—Preclinical and clinical advancements. Nat. Rev. Clin. Oncol. 2012, 9, 391–399. [Google Scholar] [CrossRef]
- Mossé, Y.P.; Lim, M.S.; Voss, S.D.; Wilner, K.; Ruffner, K.; Laliberte, J.; Rolland, D.; Balis, F.M.; Maris, J.M.; Weigel, B.J.; et al. Safety and activity of crizotinib for paediatric patients with refractory solid tumours or anaplastic large-cell lymphoma: A Children’s Oncology Group phase 1 consortium study. Lancet Oncol. 2013, 14, 472–480. [Google Scholar] [CrossRef] [PubMed]
- Weiss, B.D.; Yanik, G.; Naranjo, A.; Zhang, F.F.; Fitzgerald, W.; Shulkin, B.L.; Parisi, M.T.; Russell, H.; Grupp, S.; Pater, L.; et al. A safety and feasibility trial of (131) I-MIBG in newly diagnosed high-risk neuroblastoma: A Children’s Oncology Group study. Pediatr. Blood Cancer 2021, 68, e29117. [Google Scholar] [CrossRef]
- Alam, M.W.; Borenäs, M.; Lind, D.E.; Cervantes-Madrid, D.; Umapathy, G.; Palmer, R.H.; Hallberg, B. Alectinib, an Anaplastic Lymphoma Kinase Inhibitor, Abolishes ALK Activity and Growth in ALK-Positive Neuroblastoma Cells. Front. Oncol. 2019, 9, 579. [Google Scholar] [CrossRef]
- Cervantes-Madrid, D.; Szydzik, J.; Lind, D.E.; Borenäs, M.; Bemark, M.; Cui, J.; Palmer, R.H.; Hallberg, B. Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells. Sci. Rep. 2019, 9, 19353. [Google Scholar] [CrossRef]
- Infarinato, N.R.; Park, J.H.; Krytska, K.; Ryles, H.T.; Sano, R.; Szigety, K.M.; Li, Y.; Zou, H.Y.; Lee, N.V.; Smeal, T.; et al. The ALK/ROS1 Inhibitor PF-06463922 Overcomes Primary Resistance to Crizotinib in ALK-Driven Neuroblastoma. Cancer Discov. 2016, 6, 96–107. [Google Scholar] [CrossRef] [PubMed]
- Iyer, R.; Wehrmann, L.; Golden, R.L.; Naraparaju, K.; Croucher, J.L.; MacFarland, S.P.; Guan, P.; Kolla, V.; Wei, G.; Cam, N.; et al. Entrectinib is a potent inhibitor of Trk-driven neuroblastomas in a xenograft mouse model. Cancer Lett. 2016, 372, 179–186. [Google Scholar] [CrossRef]
- Siaw, J.T.; Wan, H.; Pfeifer, K.; Rivera, V.M.; Guan, J.; Palmer, R.H.; Hallberg, B. Brigatinib, an anaplastic lymphoma kinase inhibitor, abrogates activity and growth in ALK-positive neuroblastoma cells, Drosophila and mice. Oncotarget 2016, 7, 29011–29022. [Google Scholar] [CrossRef]
- Berko, E.R.; Witek, G.M.; Matkar, S.; Petrova, Z.O.; Wu, M.A.; Smith, C.M.; Daniels, A.; Kalna, J.; Kennedy, A.; Gostuski, I.; et al. Circulating tumor DNA reveals mechanisms of lorlatinib resistance in patients with relapsed/refractory ALK-driven neuroblastoma. Nat. Commun. 2023, 14, 2601. [Google Scholar] [CrossRef] [PubMed]
- Goldsmith, K.C.; Park, J.R.; Kayser, K.; Malvar, J.; Chi, Y.Y.; Groshen, S.G.; Villablanca, J.G.; Krytska, K.; Lai, L.M.; Acharya, P.T.; et al. Lorlatinib with or without chemotherapy in ALK-driven refractory/relapsed neuroblastoma: Phase 1 trial results. Nat. Med. 2023, 29, 1092–1102. [Google Scholar] [CrossRef]
- Suk, Y.; Singh, S.K. Safety and efficacy of lorlatinib against ALK-driven refractory or relapsed neuroblastoma. Cell Rep. Med. 2023, 4, 101071. [Google Scholar] [CrossRef] [PubMed]
- Fischer, M.; Moreno, L.; Ziegler, D.S.; Marshall, L.V.; Zwaan, C.M.; Irwin, M.S.; Casanova, M.; Sabado, C.; Wulff, B.; Stegert, M.; et al. Ceritinib in paediatric patients with anaplastic lymphoma kinase-positive malignancies: An open-label, multicentre, phase 1, dose-escalation and dose-expansion study. Lancet Oncol. 2021, 22, 1764–1776. [Google Scholar] [CrossRef]
- Stiefel, J.; Kushner, B.H.; Roberts, S.S.; Iglesias-Cardenas, F.; Kramer, K.; Modak, S. Anaplastic Lymphoma Kinase Inhibitors for Therapy of Neuroblastoma in Adults. JCO Precis. Oncol. 2023, 7, e2300138. [Google Scholar] [CrossRef] [PubMed]
- Sano, R.; Krytska, K.; Larmour, C.E.; Raman, P.; Martinez, D.; Ligon, G.F.; Lillquist, J.S.; Cucchi, U.; Orsini, P.; Rizzi, S.; et al. An antibody-drug conjugate directed to the ALK receptor demonstrates efficacy in preclinical models of neuroblastoma. Sci. Transl. Med. 2019, 11, eaau9732. [Google Scholar] [CrossRef] [PubMed]
- Olejarz, W.; Dominiak, A.; Żołnierzak, A.; Kubiak-Tomaszewska, G.; Lorenc, T. Tumor-Derived Exosomes in Immunosuppression and Immunotherapy. J. Immunol. Res. 2020, 2020, 6272498. [Google Scholar] [CrossRef] [PubMed]
- Gao, Y.; Qin, Y.; Wan, C.; Sun, Y.; Meng, J.; Huang, J.; Hu, Y.; Jin, H.; Yang, K. Small Extracellular Vesicles: A Novel Avenue for Cancer Management. Front. Oncol. 2021, 11, 638357. [Google Scholar] [CrossRef] [PubMed]
- Chen, G.; Huang, A.C.; Zhang, W.; Zhang, G.; Wu, M.; Xu, W.; Yu, Z.; Yang, J.; Wang, B.; Sun, H.; et al. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature 2018, 560, 382–386. [Google Scholar] [CrossRef] [PubMed]
- Poggio, M.; Hu, T.; Pai, C.C.; Chu, B.; Belair, C.D.; Chang, A.; Montabana, E.; Lang, U.E.; Fu, Q.; Fong, L.; et al. Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory. Cell 2019, 177, 414–427.e13. [Google Scholar] [CrossRef] [PubMed]
- Battke, C.; Ruiss, R.; Welsch, U.; Wimberger, P.; Lang, S.; Jochum, S.; Zeidler, R. Tumour exosomes inhibit binding of tumour-reactive antibodies to tumour cells and reduce ADCC. Cancer Immunol. Immunother. 2011, 60, 639–648. [Google Scholar] [CrossRef] [PubMed]
- Berchem, G.; Noman, M.Z.; Bosseler, M.; Paggetti, J.; Baconnais, S.; Le Cam, E.; Nanbakhsh, A.; Moussay, E.; Mami-Chouaib, F.; Janji, B.; et al. Hypoxic tumor-derived microvesicles negatively regulate NK cell function by a mechanism involving TGF-β and miR23a transfer. Oncoimmunology 2016, 5, e1062968. [Google Scholar] [CrossRef] [PubMed]
- Capuano, C.; Pighi, C.; Battella, S.; De Federicis, D.; Galandrini, R.; Palmieri, G. Harnessing CD16-Mediated NK Cell Functions to Enhance Therapeutic Efficacy of Tumor-Targeting mAbs. Cancers 2021, 13, 2500. [Google Scholar] [CrossRef]
- Zhao, J.; Schlößer, H.A.; Wang, Z.; Qin, J.; Li, J.; Popp, F.; Popp, M.C.; Alakus, H.; Chon, S.H.; Hansen, H.P.; et al. Tumor-Derived Extracellular Vesicles Inhibit Natural Killer Cell Function in Pancreatic Cancer. Cancers 2019, 11, 874. [Google Scholar] [CrossRef]
- Liu, X.; Wills, C.A.; Chen, L.; Zhang, J.; Zhao, Y.; Zhou, M.; Sundstrom, J.M.; Schell, T.; Spiegelman, V.S.; Young, M.M.; et al. Small extracellular vesicles induce resistance to anti-GD2 immunotherapy unveiling tipifarnib as an adjunct to neuroblastoma immunotherapy. J. ImmunoTherapy Cancer 2022, 10, e004399. [Google Scholar] [CrossRef]
- Ho, A.L.; Brana, I.; Haddad, R.; Bauman, J.; Bible, K.; Oosting, S.; Wong, D.J.; Ahn, M.-J.; Boni, V.; Even, C.; et al. Tipifarnib in Head and Neck Squamous Cell Carcinoma With HRAS Mutations. J. Clin. Oncol. 2021, 39, 1856–1864. [Google Scholar] [CrossRef]
- Otto, T.; Horn, S.; Brockmann, M.; Eilers, U.; Schüttrumpf, L.; Popov, N.; Kenney, A.M.; Schulte, J.H.; Beijersbergen, R.; Christiansen, H.; et al. Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma. Cancer Cell 2009, 15, 67–78. [Google Scholar] [CrossRef]
- Shang, X.; Burlingame, S.M.; Okcu, M.F.; Ge, N.; Russell, H.V.; Egler, R.A.; David, R.D.; Vasudevan, S.A.; Yang, J.; Nuchtern, J.G. Aurora A is a negative prognostic factor and a new therapeutic target in human neuroblastoma. Mol. Cancer Ther. 2009, 8, 2461–2469. [Google Scholar] [CrossRef] [PubMed]
- Brockmann, M.; Poon, E.; Berry, T.; Carstensen, A.; Deubzer, H.E.; Rycak, L.; Jamin, Y.; Thway, K.; Robinson, S.P.; Roels, F.; et al. Small molecule inhibitors of aurora-a induce proteasomal degradation of N-myc in childhood neuroblastoma. Cancer Cell 2013, 24, 75–89. [Google Scholar] [CrossRef] [PubMed]
- Rishfi, M.; Krols, S.; Martens, F.; Bekaert, S.L.; Sanders, E.; Eggermont, A.; De Vloed, F.; Goulding, J.R.; Risseeuw, M.; Molenaar, J.; et al. Targeted AURKA degradation: Towards new therapeutic agents for neuroblastoma. Eur. J. Med. Chem. 2023, 247, 115033. [Google Scholar] [CrossRef]
- Chu, Q.S.; Bouganim, N.; Fortier, C.; Zaknoen, S.; Stille, J.R.; Kremer, J.D.; Yuen, E.; Hui, Y.H.; de la Peña, A.; Lithio, A.; et al. Aurora kinase A inhibitor, LY3295668 erbumine: A phase 1 monotherapy safety study in patients with locally advanced or metastatic solid tumors. Investig. N. Drugs 2021, 39, 1001–1010. [Google Scholar] [CrossRef]
- Michaelis, M.; Selt, F.; Rothweiler, F.; Löschmann, N.; Nüsse, B.; Dirks, W.G.; Zehner, R.; Cinatl, J., Jr. Aurora kinases as targets in drug-resistant neuroblastoma cells. PLoS ONE 2014, 9, e108758. [Google Scholar] [CrossRef] [PubMed]
- Mossé, Y.P.; Fox, E.; Teachey, D.T.; Reid, J.M.; Safgren, S.L.; Carol, H.; Lock, R.B.; Houghton, P.J.; Smith, M.A.; Hall, D.; et al. A Phase II Study of Alisertib in Children with Recurrent/Refractory Solid Tumors or Leukemia: Children’s Oncology Group Phase I and Pilot Consortium (ADVL0921). Clin. Cancer Res. 2019, 25, 3229–3238. [Google Scholar] [CrossRef]
- Mossé, Y.P.; Lipsitz, E.; Fox, E.; Teachey, D.T.; Maris, J.M.; Weigel, B.; Adamson, P.C.; Ingle, M.A.; Ahern, C.H.; Blaney, S.M. Pediatric phase I trial and pharmacokinetic study of MLN8237, an investigational oral selective small-molecule inhibitor of Aurora kinase A: A Children’s Oncology Group Phase I Consortium study. Clin. Cancer Res. 2012, 18, 6058–6064. [Google Scholar] [CrossRef]
- DuBois, S.G.; Marachelian, A.; Fox, E.; Kudgus, R.A.; Reid, J.M.; Groshen, S.; Malvar, J.; Bagatell, R.; Wagner, L.; Maris, J.M.; et al. Phase I Study of the Aurora A Kinase Inhibitor Alisertib in Combination With Irinotecan and Temozolomide for Patients With Relapsed or Refractory Neuroblastoma: A NANT (New Approaches to Neuroblastoma Therapy) Trial. J. Clin. Oncol. 2016, 34, 1368–1375. [Google Scholar] [CrossRef] [PubMed]
- DuBois, S.G.; Mosse, Y.P.; Fox, E.; Kudgus, R.A.; Reid, J.M.; McGovern, R.; Groshen, S.; Bagatell, R.; Maris, J.M.; Twist, C.J.; et al. Phase II Trial of Alisertib in Combination with Irinotecan and Temozolomide for Patients with Relapsed or Refractory Neuroblastoma. Clin. Cancer Res. 2018, 24, 6142–6149. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.; Sheng, Y.; Sun, D.; Sun, J.; Li, L.; Sun, L. AURKB promotes tumorigenesis and carboplatin resistance by regulating the ERK pathway in neuroblastoma cells. Int. J. Neurosci. 2023, 133, 1224–1232. [Google Scholar] [CrossRef] [PubMed]
- Casey, D.L.; Cheung, N.V. Immunotherapy of Pediatric Solid Tumors: Treatments at a Crossroads, with an Emphasis on Antibodies. Cancer Immunol. Res. 2020, 8, 161–166. [Google Scholar] [CrossRef] [PubMed]
- Galluzzi, L.; Chan, T.A.; Kroemer, G.; Wolchok, J.D.; López-Soto, A. The hallmarks of successful anticancer immunotherapy. Sci Transl Med. 2018, 10, eaat7807. [Google Scholar] [CrossRef] [PubMed]
- Le, T.P.; Thai, T.H. The State of Cellular Adoptive Immunotherapy for Neuroblastoma and Other Pediatric Solid Tumors. Front. Immunol. 2017, 8, 1640. [Google Scholar] [CrossRef] [PubMed]
- Ahmed, N.; Brawley, V.S.; Hegde, M.; Robertson, C.; Ghazi, A.; Gerken, C.; Liu, E.; Dakhova, O.; Ashoori, A.; Corder, A.; et al. Human Epidermal Growth Factor Receptor 2 (HER2) -Specific Chimeric Antigen Receptor-Modified T Cells for the Immunotherapy of HER2-Positive Sarcoma. J. Clin. Oncol. 2015, 33, 1688–1696. [Google Scholar] [CrossRef] [PubMed]
- Louis, C.U.; Savoldo, B.; Dotti, G.; Pule, M.; Yvon, E.; Myers, G.D.; Rossig, C.; Russell, H.V.; Diouf, O.; Liu, E.; et al. Antitumor activity and long-term fate of chimeric antigen receptor-positive T cells in patients with neuroblastoma. Blood 2011, 118, 6050–6056. [Google Scholar] [CrossRef] [PubMed]
- Pule, M.A.; Savoldo, B.; Myers, G.D.; Rossig, C.; Russell, H.V.; Dotti, G.; Huls, M.H.; Liu, E.; Gee, A.P.; Mei, Z.; et al. Virus-specific T cells engineered to coexpress tumor-specific receptors: Persistence and antitumor activity in individuals with neuroblastoma. Nat. Med. 2008, 14, 1264–1270. [Google Scholar] [CrossRef]
- Del Bufalo, F.; De Angelis, B.; Caruana, I.; Del Baldo, G.; De Ioris, M.A.; Serra, A.; Mastronuzzi, A.; Cefalo, M.G.; Pagliara, D.; Amicucci, M.; et al. GD2-CART01 for Relapsed or Refractory High-Risk Neuroblastoma. N. Engl. J. Med. 2023, 388, 1284–1295. [Google Scholar] [CrossRef]
- Straathof, K.; Flutter, B.; Wallace, R.; Jain, N.; Loka, T.; Depani, S.; Wright, G.; Thomas, S.; Cheung, G.W.; Gileadi, T.; et al. Antitumor activity without on-target off-tumor toxicity of GD2-chimeric antigen receptor T cells in patients with neuroblastoma. Sci. Transl. Med. 2020, 12, eabd6169. [Google Scholar] [CrossRef] [PubMed]
- Martinsson, T.; Eriksson, T.; Abrahamsson, J.; Caren, H.; Hansson, M.; Kogner, P.; Kamaraj, S.; Schönherr, C.; Weinmar, J.; Ruuth, K.; et al. Appearance of the novel activating F1174S ALK mutation in neuroblastoma correlates with aggressive tumor progression and unresponsiveness to therapy. Cancer Res. 2011, 71, 98–105. [Google Scholar] [CrossRef] [PubMed]
- Walker, A.J.; Majzner, R.G.; Zhang, L.; Wanhainen, K.; Long, A.H.; Nguyen, S.M.; Lopomo, P.; Vigny, M.; Fry, T.J.; Orentas, R.J.; et al. Tumor Antigen and Receptor Densities Regulate Efficacy of a Chimeric Antigen Receptor Targeting Anaplastic Lymphoma Kinase. Mol. Ther. 2017, 25, 2189–2201. [Google Scholar] [CrossRef] [PubMed]
- Bergaggio, E.; Tai, W.T.; Aroldi, A.; Mecca, C.; Landoni, E.; Nüesch, M.; Mota, I.; Metovic, J.; Molinaro, L.; Ma, L.; et al. ALK inhibitors increase ALK expression and sensitize neuroblastoma cells to ALK.CAR-T cells. Cancer Cell 2023, 41, 2100–2116.e10. [Google Scholar] [CrossRef] [PubMed]
- Schmelz, K.; Toedling, J.; Huska, M.; Cwikla, M.C.; Kruetzfeldt, L.-M.; Proba, J.; Ambros, P.F.; Ambros, I.M.; Boral, S.; Lodrini, M.; et al. Spatial and temporal intratumour heterogeneity has potential consequences for single biopsy-based neuroblastoma treatment decisions. Nat. Commun. 2021, 12, 6804. [Google Scholar] [CrossRef] [PubMed]
- Chang, D.H.; Osman, K.; Connolly, J.; Kukreja, A.; Krasovsky, J.; Pack, M.; Hutchinson, A.; Geller, M.; Liu, N.; Annable, R.; et al. Sustained expansion of NKT cells and antigen-specific T cells after injection of alpha-galactosyl-ceramide loaded mature dendritic cells in cancer patients. J. Exp. Med. 2005, 201, 1503–1517. [Google Scholar] [CrossRef] [PubMed]
- Metelitsa, L.S.; Wu, H.W.; Wang, H.; Yang, Y.; Warsi, Z.; Asgharzadeh, S.; Groshen, S.; Wilson, S.B.; Seeger, R.C. Natural killer T cells infiltrate neuroblastomas expressing the chemokine CCL2. J. Exp. Med. 2004, 199, 1213–1221. [Google Scholar] [CrossRef]
- Motohashi, S.; Okamoto, Y.; Yoshino, I.; Nakayama, T. Anti-tumor immune responses induced by iNKT cell-based immunotherapy for lung cancer and head and neck cancer. Clin. Immunol. 2011, 140, 167–176. [Google Scholar] [CrossRef]
- Heczey, A.; Liu, D.; Tian, G.; Courtney, A.N.; Wei, J.; Marinova, E.; Gao, X.; Guo, L.; Yvon, E.; Hicks, J.; et al. Invariant NKT cells with chimeric antigen receptor provide a novel platform for safe and effective cancer immunotherapy. Blood 2014, 124, 2824–2833. [Google Scholar] [CrossRef] [PubMed]
- Rotolo, A.; Caputo, V.S.; Holubova, M.; Baxan, N.; Dubois, O.; Chaudhry, M.S.; Xiao, X.; Goudevenou, K.; Pitcher, D.S.; Petevi, K.; et al. Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting. Cancer Cell 2018, 34, 596–610.e11. [Google Scholar] [CrossRef]
- Heczey, A.; Courtney, A.N.; Montalbano, A.; Robinson, S.; Liu, K.; Li, M.; Ghatwai, N.; Dakhova, O.; Liu, B.; Raveh-Sadka, T.; et al. Anti-GD2 CAR-NKT cells in patients with relapsed or refractory neuroblastoma: An interim analysis. Nat. Med. 2020, 26, 1686–1690. [Google Scholar] [CrossRef] [PubMed]
- Heczey, A.; Xu, X.; Courtney, A.N.; Tian, G.; Barragan, G.A.; Guo, L.; Amador, C.M.; Ghatwai, N.; Rathi, P.; Wood, M.S.; et al. Anti-GD2 CAR-NKT cells in relapsed or refractory neuroblastoma: Updated phase 1 trial interim results. Nat. Med. 2023, 29, 1379–1388. [Google Scholar] [CrossRef] [PubMed]
Type | Rationale | Example | Relevant Trial Identifier/Reference |
---|---|---|---|
Anti-GD2 mAb | Augmenting the immunotherapeutic effects of anti-GD2 mAb in combination with chemotherapies, and/or other immunotherapies | Dinutuximab + IL-2 + GM-CSF | [102,107] |
Dinutuximab + lenalidomide + retinoic acid | NCT01711554 | ||
Dinutuximab beta + conventional chemotherapy | NCT01701479 | ||
Dinutuximab + magrolimab (anti-CD47) | NCT04751383 | ||
Dinutuximab + lenalidomide + expanded autologous NK cells | NCT02573896 | ||
Hu14.18-IL2 + expanded haploidentical NK cells | NCT03209869 | ||
Dinutuximab beta + IL-2 | NCT02258815 | ||
Dinutuximab beta + anti-CD11b | [115] | ||
14.G2a + vorinostat | [118] | ||
Dinutuximab beta + nivolumab (anti-PD1) + 131I-MIBG | NCT02914405 | ||
Anti-B7-H3 | Targeting NBL-tumor cells with restricted expression on normal cells, reducing major side effects | Anti-B7-H3 mAb | [108] |
Bispecific antibody of GD2 and B7-H3 | [110] | ||
ALK inhibition | ALK mutations correlated with poor NBL prognosis | Crizotinib | NCT03126916 |
Lorlatinib with chemotherapy | [158] | ||
AURKA inhibition | Heightened expression of AURKA correlated with MYCN amplification and overall survival in NBL patients | SK2188 | [176] |
Alisertib + Irinotecan + Temozolomi | [181,182] | ||
ICI | Countering adaptive immune resistance | Anti-PD-1 and anti-CTLA-4 with cyclophosphamide | [37] |
BLZ945 (CSF-1R inhibitor) + PD-1/PD-L1 blocking antibodies | [112] | ||
Anti-PD-1 and anti-CTLA-4 with whole tumor cell vaccination | [126] | ||
CAR | CARs combine the epitope specificity of a monoclonal antibody with the cytolytic potential of an activated T cell, enabling the targeting of tumors expressing the corresponding cell surface antigen independently of MHC presentation | Anti-GD2 CAR-NKT cell | NCT03294954 |
CAR T cells targeting B7-H3 | [109] | ||
NKG2D.ζ-NK cells + CAR-T cells | [117] | ||
ALK.CAR-T cell + lorlatinib | [194] | ||
Angiogenesis inhibition | Vascular complexity correlates with the aggressiveness in human NBL | Bevacizumab (anti-VEGF) + chemotherapy | [85] |
mPGES-1 inhibitor | [69] |
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Mao, C.; Poimenidou, M.; Craig, B.T. Current Knowledge and Perspectives of Immunotherapies for Neuroblastoma. Cancers 2024, 16, 2865. https://doi.org/10.3390/cancers16162865
Mao C, Poimenidou M, Craig BT. Current Knowledge and Perspectives of Immunotherapies for Neuroblastoma. Cancers. 2024; 16(16):2865. https://doi.org/10.3390/cancers16162865
Chicago/Turabian StyleMao, Chenkai, Maria Poimenidou, and Brian T. Craig. 2024. "Current Knowledge and Perspectives of Immunotherapies for Neuroblastoma" Cancers 16, no. 16: 2865. https://doi.org/10.3390/cancers16162865