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

Bulletin du cancer
Tilda PassatJaafar Bennouna

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 interleukine-17 (IL-17). These two mechanisms are res...Continue Reading

Citations

Nov 16, 2019·Journal for Immunotherapy of Cancer·Satya Das, Douglas B Johnson
Aug 23, 2020·International Journal of Molecular Sciences·Ana BocanegraGrazyna Kochan
Oct 9, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yi-He LiuPeng Zhang
Nov 26, 2020·OncoTargets and Therapy·Tian-Ming CuiLian-Xin Liu
Mar 7, 2021·Joint, Bone, Spine : Revue Du Rhumatisme·Leslie AddaAlice Séjourné
Jun 10, 2021·Journal of Hepatocellular Carcinoma·Cecilia MongeTim F Greten
Jul 14, 2021·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Carolina A FerreiraUmar Mahmood

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