CD27 is a member of the tumor necrosis factor receptor superfamily.[5] It is currently of interest to immunologists as a co-stimulatory immune checkpoint molecule, and is the target of an anti-cancer drug in clinical trials.[6]
Expression
editDuring mouse embryonic development, specific (medium) expression levels of CD27 (in addition to high cKit,[7][8] medium Gata2,[9][10][8] and high CD31[8] expression levels) define the very first adult definitive hematopoietic stem cells generated in the aorta-gonad-mesonephros region.[8] Furthermore, CD27 is expressed on both naïve and activated effector T cells as well as NK cells and activated B cells.[5] It is a type I transmembrane protein with cysteine-rich domains, but once T cells have become activated, a soluble form of CD27 can be shed.[5][6]
Function
editThe protein encoded by this gene is a member of the TNF-receptor superfamily.[11] This receptor is required for generation and long-term maintenance of T cell immunity. It binds to ligand CD70, and plays a key role in regulating B-cell activation and immunoglobulin synthesis.[5]
When CD27 binds CD70, a signaling cascade leads to the differentiation and clonal expansion of T cells.[11] The cascade also results in improved survival and memory of cytotoxic T cells and increased production of certain cytokines.[12] This receptor transduces signals that lead to the activation of NF-κB and MAPK8/JNK.[11] Adaptor proteins TRAF2, TRAF3, and TRAF5 have been shown to mediate the signaling process of this receptor via ubiquitination.[5][6] CD27-binding protein (SIVA), a proapoptotic protein, can bind to this receptor and is thought to play an important role in the apoptosis induced by this receptor.[13]
In murine γδ T cells its expression has been correlated with the secretion of IFNγ.[14]
Clinical significance
editAs a drug target
editVarlilumab is an IgG1 antibody that binds to CD27 and is an experimental cancer treatment.[6] This agonist antibody stimulates CD27 when it binds.[6] The drug is in early clinical trials and appears to stimulate T cells and increase production of cytokines such as interferon-gamma.[6][11]
Interactions
editCD27 has been shown to interact with SIVA1,[15] TRAF2[16][17] and TRAF3.[16][17]
Mutations
editSome mutations can decrease the expression of CD27. Three such mutations, C53Y, C96Y, and R107C, are located in the cysteine-rich domains of CD27.[5]
References
edit- ^ a b c GRCh38: Ensembl release 89: ENSG00000139193 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030336 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c d e f Buchan SL, Rogel A, Al-Shamkhani A (January 2018). "The immunobiology of CD27 and OX40 and their potential as targets for cancer immunotherapy". Blood. 131 (1): 39–48. doi:10.1182/blood-2017-07-741025. PMID 29118006.
- ^ a b c d e f Sturgill ER (November 2017). "TNFR agonists: a review of current biologics targeting OX40, 4-1BB, CD27, and GITR". American Journal of Hematology/Oncology. 13 (11): 4–15.
- ^ Sánchez MJ, Holmes A, Miles C, Dzierzak E (December 1996). "Characterization of the first definitive hematopoietic stem cells in the AGM and liver of the mouse embryo". Immunity. 5 (6): 513–25. doi:10.1016/s1074-7613(00)80267-8. PMID 8986712.
- ^ a b c d Vink CS, Calero-Nieto FJ, Wang X, Maglitto A, Mariani SA, Jawaid W, et al. (May 2020). "Iterative Single-Cell Analyses Define the Transcriptome of the First Functional Hematopoietic Stem Cells". Cell Reports. 31 (6): 107627. doi:10.1016/j.celrep.2020.107627. PMC 7225750. PMID 32402290.
- ^ Kaimakis P, de Pater E, Eich C, Solaimani Kartalaei P, Kauts ML, Vink CS, et al. (March 2016). "Functional and molecular characterization of mouse Gata2-independent hematopoietic progenitors". Blood. 127 (11): 1426–37. doi:10.1182/blood-2015-10-673749. PMC 4797020. PMID 26834239.
- ^ Eich C, Arlt J, Vink CS, Solaimani Kartalaei P, Kaimakis P, Mariani SA, et al. (January 2018). "In vivo single cell analysis reveals Gata2 dynamics in cells transitioning to hematopoietic fate". The Journal of Experimental Medicine. 215 (1): 233–248. doi:10.1084/jem.20170807. PMC 5748852. PMID 29217535.
- ^ a b c d Burugu S, Dancsok AR, Nielsen TO (October 2018). "Emerging targets in cancer immunotherapy". Seminars in Cancer Biology. Immuno-oncological biomarkers. 52 (Pt 2): 39–52. doi:10.1016/j.semcancer.2017.10.001. PMID 28987965. S2CID 33534342.
- ^ Bullock TN (April 2017). "Stimulating CD27 to quantitatively and qualitatively shape adaptive immunity to cancer". Current Opinion in Immunology. 45: 82–88. doi:10.1016/j.coi.2017.02.001. PMC 5449212. PMID 28319731.
- ^ "Entrez Gene: CD27 CD27 molecule".
- ^ Ribot JC, deBarros A, Pang DJ, Neves JF, Peperzak V, Roberts SJ, et al. (April 2009). "CD27 is a thymic determinant of the balance between interferon-gamma- and interleukin 17-producing gammadelta T cell subsets". Nature Immunology. 10 (4): 427–36. doi:10.1038/ni.1717. PMC 4167721. PMID 19270712.
- ^ Prasad KV, Ao Z, Yoon Y, Wu MX, Rizk M, Jacquot S, Schlossman SF (June 1997). "CD27, a member of the tumor necrosis factor receptor family, induces apoptosis and binds to Siva, a proapoptotic protein". Proceedings of the National Academy of Sciences of the United States of America. 94 (12): 6346–51. Bibcode:1997PNAS...94.6346P. doi:10.1073/pnas.94.12.6346. PMC 21052. PMID 9177220.
- ^ a b Yamamoto H, Kishimoto T, Minamoto S (November 1998). "NF-kappaB activation in CD27 signaling: involvement of TNF receptor-associated factors in its signaling and identification of functional region of CD27". Journal of Immunology. 161 (9): 4753–9. doi:10.4049/jimmunol.161.9.4753. PMID 9794406. S2CID 22442601.
- ^ a b Akiba H, Nakano H, Nishinaka S, Shindo M, Kobata T, Atsuta M, et al. (May 1998). "CD27, a member of the tumor necrosis factor receptor superfamily, activates NF-kappaB and stress-activated protein kinase/c-Jun N-terminal kinase via TRAF2, TRAF5, and NF-kappaB-inducing kinase". The Journal of Biological Chemistry. 273 (21): 13353–8. doi:10.1074/jbc.273.21.13353. PMID 9582383.
Further reading
edit- Lens SM, de Jong R, Hintzen RQ, Koopman G, van Lier RA, van Oers RH (June 1995). "CD27-CD70 interaction: unravelling its implication in normal and neoplastic B-cell growth". Leukemia & Lymphoma. 18 (1–2): 51–9. doi:10.3109/10428199509064922. PMID 8580829.
- Agematsu K (April 2000). "Memory B cells and CD27". Histology and Histopathology. 15 (2): 573–6. doi:10.14670/HH-15.573. PMID 10809378.
- van Baarle D, Kostense S, van Oers MH, Hamann D, Miedema F (December 2002). "Failing immune control as a result of impaired CD8+ T-cell maturation: CD27 might provide a clue". Trends in Immunology. 23 (12): 586–91. doi:10.1016/S1471-4906(02)02326-8. PMID 12464570.
- Dörner T, Lipsky PE (2005). "Correlation of circulating CD27high plasma cells and disease activity in systemic lupus erythematosus". Lupus. 13 (5): 283–9. doi:10.1191/0961203304lu1014oa. PMID 15230280. S2CID 34654758.
External links
edit- CD27+Antigens at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Human CD27 genome location and CD27 gene details page in the UCSC Genome Browser.
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