Hypothesis for the development of immune-related adverse events in immune checkpoint inhibitors 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.

Keywords

• irAEs - immune-related adverse events
• ICIs - immune checkpoint inhibitors
• Predisposing factors
• Paraneoplastic syndrome
• Gut dysbacteriosis
• Cancer autoimmunity