checkpoint inhibitors
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In the classification and typing of breast cancer, triple-negative breast cancer (TNBC) is one type of refractory breast cancer, while chemotherapy stays in the traditional treatment methods. However, the impact of chemotherapy is short-lived and may lead to recurrence due to incomplete killing of tumor cells. The occurrence, development, and relapse of breast cancer are relevant to T cell dysfunction, multiplied expression of related immune checkpoint molecules (ICIs) such as programmed death receptor 1 (PD-1), programmed cell death 1 ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) produce immunosuppressive effect. Immunotherapy (namely, immune checkpoint inhibitors, adoptive cellular immunotherapy, CAR-T immunotherapy and some potential treatments) provides new hope in TNBC. This review focuses on the new immune strategies of TNBC patients.

Autoimmune and paraneoplastic encephalitides represent an increasingly recognized cause of devastating human illness as well as an emerging area of neurological injury associated with immune checkpoint inhibitors. Two groups of antibodies have been detected in affected patients. Antibodies in the first group are directed against neuronal cell surface membrane proteins and are exemplified by antibodies directed against the N-methyl-D-aspartate receptor (anti-NMDAR), found in patients with autoimmune encephalitis, and antibodies directed against the leucine-rich glioma-inactivated 1 protein (anti-LGI1), associated with faciobrachial dystonic seizures and limbic encephalitis. Antibodies in this group produce non-lethal neuronal dysfunction, and their associated conditions often respond to treatment. Antibodies in the second group, as exemplified by anti-Yo antibody, found in patients with rapidly progressive cerebellar syndrome, and anti-Hu antibody, associated with encephalomyelitis, react with intracellular neuronal antigens. These antibodies are characteristically found in patients with underlying malignancy, and neurological impairment is the result of neuronal death. Within the last few years, major advances have been made in understanding the pathogenesis of neurological disorders associated with antibodies against neuronal cell surface antigens. In contrast, the events that lead to neuronal death in conditions associated with antibodies directed against intracellular antigens, such as anti-Yo and anti-Hu, remain poorly understood, and the respective roles of antibodies and T lymphocytes in causing neuronal injury have not been defined in an animal model. In this review, we discuss current knowledge of these two groups of antibodies in terms of their discovery, how they arise, the interaction of both types of antibodies with their molecular targets, and the attempts that have been made to reproduce human neuronal injury in tissue culture models and experimental animals. We then discuss the emerging area of autoimmune neuronal injury associated with immune checkpoint inhibitors and the implications of current research for the treatment of affected patients.

Prostate cancer (PC) is the most common malignancy and the fifth cause of cancer death in men. The treatment for localized or locally advanced stages offers a high probability of cure. Even though the therapeutic landscape has significantly improved over the last decade, metastatic PC (mPC) still has a poor prognosis mainly due to the development of therapy resistance. In this context, the use of immunotherapy alone or in combination with other drugs has been explored in recent years. However, T-cell directed immune checkpoint inhibitors (ICIs) have shown limited activity with inconclusive results in mPC patients, most likely due to the highly immunosuppressive PC tumor microenvironment (TME). In this scenario, targeting macrophages, a highly abundant immunosuppressive cell type in the TME, could offer a new therapeutic strategy to improve immunotherapy efficacy. In this review, we summarize the growing field of macrophage-directed immunotherapies and discuss how these could be applied in the treatment of mPC, focusing on their combination with ICIs.

AbstractAnti-CTLA-4 and anti-PD-1/PD-L1 immune checkpoint inhibitors are therapeutic monoclonal antibodies that do not target cancer cells but are designed to reactivate or promote antitumor immunity. Dosing and scheduling of these biologics were established according to conventional drug development models, even though the determination of a maximum tolerated dose in the clinic could only be defined for anti-CTLA-4. Given the pharmacology of these monoclonal antibodies, their high interpatient pharmacokinetic variability, the actual clinical benefit as monotherapy that is observed only in a specific subset of patients, and the substantial cost of these treatments, a number of questions arise regarding the selected dose and the dosing interval. This review aims to outline the development of these immunotherapies and considers optimization options that could be used in clinical practice.

Background: Several studies reported improved outcomes with conventional treatments (CT, i.e., chemotherapy ± targeted therapy) administered after immune checkpoints inhibitors (ICI) in certain tumor types. No data are available concerning patients (pts) with metastatic colorectal cancer (mCRC) harboring mismatch repair deficiency/microsatellite instability (dMMR/MSI). We aimed to assess the outcomes of dMMR/MSI mCRC pts receiving CT after ICI failure. Methods: We conducted a retrospective multicenter study investigating the outcomes of all dMMR/MSI mCRC pts who received post-ICI CT between 2015 and 2020. Results: 31 pts (male 61%, median age 56 years) were included. ICI was an anti-PD(L)1 monotherapy in 71% of pts, and 61% received >2 lines before post-ICI CT. The overall response rate and disease control rate were 13% and 45%, with a median progression-free survival (PFS) and overall survival of 2.9 and 7.4 months, respectively. No association of the outcomes with either ICI efficacy or anti-angiogenic agents was observed. Prolonged PFS (range 16.1–21.3 months) was observed in 4 pts (13%). Conclusions: Although conducted on a limited number of patients, our results do not support an association of previous ICI treatment with an enhanced efficacy of CT in dMMR/MSI mCRC. However, prolonged disease control was observed in several cases, suggesting that some pts might derive an unexpected benefit from post-ICI treatments.

Immune checkpoint inhibitors, which promote or suppress the anti-tumor immune response, are becoming the mainstay of cancer treatment. In 2018, CheckMate 214 study showed a higher response rate with ipilimumab and nivolumab combination therapy compared to conventional therapy for advanced renal cell carcinoma. We report a case of complete response and durable response for two years to ipilimumab and nivolumab combination therapy in a patient with postoperative renal cancer recurrence that caused immune-related adverse events such as interstitial pneumonia and hepatotoxicity.

Background: The treatment options for GEP-NENs includes various drugs and is based on grading, morphology and location of the primary Objective: The aim of our work is to investigate the clinical impact of new immune checkpoint inhibitors in order to define a new possible strategy of use within GEP-NENs. Method: A scientific literature search from 2015 to January 2020 was performed by using PubMed and Embase: reviews and prospective or retrospective studies with a minimum of twenty patients were selected; conference proceedings were included Results: several studies have been conducted to assess the role of immune checkpoint inhibitors in NENs, but nowadays the current knowledge in this field is mainly based on a phase I-II studies. Immunotherapy showed limited antitumor activity, but higher response rate was reported in poor-differentiated neuroendocrine tumors. No specific biomarkers were identified for patient selection and response assessment Conclusion: Immunotherapy appears as a powerful possibility to help our patients, but nowadays we see many gaps in this field. We must balance therapeutic possibility offered by precision oncology with the understanding the limitations of application of testing and treatment in clinical practice. Future efforts should focus on research of the best patients to candidate for immunotherapy in term of disease characteristics and previous treatments, and how to select them with accurate biomarkers.