[Physiopathological mechanisms of immune-related adverse events induced by anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies in cancer treatment].

[Physiopathological mechanisms of immune-related adverse events induced by anti-CTLA-4, anti-PD-1 and anti-PD-L1 antibodies in cancer treatment]. Bull Cancer. 2018 Sep 20;: Authors: Passat T, Touchefeu Y, Gervois N, Jarry A, Bossard C, Bennouna J Abstract Recently, the emergence of anti-CTLA-4 and anti-PD-1/PD-L1 antibodies called immune check-point inhibitors (ICPI) has modified the landscape of anti-cancer treatments. These therapeutics are associated with immune related adverse events that affect many organs, most commonly skin, digestive tract, endocrine glands and lungs. This review summarizes the main physiopathological hypotheses on the mechanisms of these toxicities. In most cases, the T lymphocytes hyperactivation induced by ICPI generates a specific response directed against tumor antigens, leading to anti-tumor activity in tumor tissues but also side effects in normal tisues called "on-target". The CD8+ cytotoxic T lymphocytes-mediated cell lysis induces the release of neoantigens, tumor antigens and auto-antigens from normal tissues, respectively. This phenomenon called "epitope spreading" leads to diversification of the T cell repertoire and thus to reduced immune tolerance, which is exacerbated by inhibition of regulator T lymphocytes. Furthermore, the predominant activation of Th1 and Th17T lymphocytes mediated by ICPI induced an increased production of pro-inflammatory cytokines such as interferon-γ (IFNγ) and inter...
Source: Bulletin du Cancer - Category: Cancer & Oncology Authors: Tags: Bull Cancer Source Type: research