Safety and Tolerability of Immune Checkpoint Inhibitors (PD-1 and PD-L1) in Cancer

Abstract

Immunotherapy has emerged in recent years and has revolutionized the treatment of cancer. Immune checkpoint inhibitors, including anti-cytotoxic T lymphocyte antigen-4 (CTLA-4), anti-programmed cell death-1 (PD-1) and anti-programmed cell death ligand-1 (PD-L1) agents, are the first of this new generation of treatments. Anti-PD-1/PD-L1 agents target immune cells by blocking the PD-1/PD-L1 pathway. This blockade leads to enhancement of the immune system and therefore restores the tumour-induced immune deficiency selectively in the tumour microenvironment. However, this shift in the balance of the immune system can also produce adverse effects that involve multiple organs. The pattern of toxicity is different from traditional chemotherapy agents or targeted therapy, and there is still little experience in recognizing and managing it. Thus, toxicity constitutes a real clinical management challenge and any new alteration should be suspected of being treatmentrelated. The most common toxicities occur in the skin, gastrointestinal tract, lungs, and endocrine, musculoskeletal, renal, nervous, haematologic, cardiovascular and ocular systems. Immune-mediated toxic effects are usually manageable, but toxicities may sometimes lead to treatment withdrawal, and even fulminant and fatal events can occur. Oncologists need to collaborate with internists, clinical immunologists and other specialists to understand, manage and prevent toxicity derived from immunotherapy. This review focuses on the mechanisms of toxicity of anti-PD-1/PD-L1 agents, and its diagnosis and management.

Identification of hub genes in cervical cancer using weighted gene co-expression network analysis

“…Tumor immunotherapy is an anticancer therapy with the goal of activating the immune system in the hope that its own immune function would inhibit tumor tissues [27]. At present, tumor immunotherapy has been shown to have strong antitumor activities in some tumor types, including melanoma and nonsmall cell lung cancer, and tumor immunotherapy drugs are clinically applied [28][29][30].…”

CIMT 2019: report on the 17th Annual Meeting of the Association for Cancer Immunotherapy

“…39 He closed his talk, showing that Nivolumab and Ipilimumab treatment is efficient against advanced melanoma, but can lead to immune-related adverse events in these patients. 40,41 As a solution, he presented a prophylactic treatment with clinically available TNF inhibitors which led to less immune-related adverse events after CTLA-4 and PD-1 monoclonal antibody treatment in human colon cancer xenograft mice, while retaining the antitumoral effect. 42 Ugur Sahin (TRON -Translational Oncology, and BioNTech SE, Mainz, Germany) opened his talk asking whether tumor antigens derived from mutations (neoantigens) or shared nonmutated tumor antigens are more suitable for the design of a therapeutic vaccine.…”

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