Hypothesis for the development of immune-related adverse events in immune checkpoint inhibitors therapy. (2022)

• Record Type: Journal Article
• Authors: Orlova, Rashida; Zhukova, Natalia; Malkova, Anna; Shoenfeld, Yehuda
• Is Part Of: Cancer treatment and research communications. Number 31(2022)
• Publication Date: 2022
• Subjects: irAEs - immune-related adverse events -- ICIs - immune checkpoint inhibitors -- Predisposing factors -- Paraneoplastic syndrome -- Gut dysbacteriosis -- Cancer autoimmunity; AG antigens -- ANA antinuclear antibodies -- anti-dsDNA antibodies to dsDNA -- ASIA adjuvant-induced autoimmune/pro-inflammatory syndrome -- CTLA-4 cytotoxic T-lymphocyte-associated protein 4 -- HLA human leukocyte antigens -- ICIs immune checkpoint inhibitors -- IFN-γ interferon gamma -- IL interleukins -- irAEs immune-related adverse events -- PD-1 a programmed cell death receptor-1 -- PD-L1 ligand of programmed cell death receptor-1 -- PNS paraneoplastic syndrome -- RF rheumatoid factor
• DOI: 10.1016/j.ctarc.2022.100529
• Languages: English
• ISSNs: 2468-2942

Abstract

Highlights: Most likely, the difference in the types of irAEs lies in the degree of specificity of ICI. For the development of specific types of irAEs, a complex of predisposing factors is required. We assume that HLA genotypes may play the key role. The high percentage of lesions of the gastrointestinal tract and skin can be explained by the presence of dysbacteriosis in patients before treatment and developed during the treatment. High percentage of thyroiditis with anti-PD1 therapy can be explained by the expression of PD-L1 in the thyroid gland. One of the types of irAEs can be a worsening of previous PNS, which are enhanced during therapy. Abstract: There are no explanations for the diversity in the development of certain immune-related adverse events (irAEs) with immune checkpoint inhibitors (ICI). The goal of this study is to search for possible predisposing factors that contribute to the development of certain autoimmune complications during anti-CTLA4 and anti-PD1/PD-L1 therapy. According to the keywords "checkpoint inhibitors, anti-CTLA4, anti-PD1/PD-L1, immune adverse events, paraneoplastic syndrome" the review and original articles published in the international databases to 2021were selected and studied. According to the analysis of the published papers, we consider that a key role in the difference in the types of irAEs lies in the specificity of the drug. The high prevalence of skin and gastrointestinal autoimmune complications can be explained by the presence of gut dysbacteriosis in patients before treatment and developed during the treatment. For the development of specific types of irAEs, a complex of predisposing factors is required, such as HLA-genotype, paraneoplastic syndromes, and the expression of PD-L1 in the thyroid gland in the case of anti-PD1 therapy.