Molecular Pathology of Immune Checkpoint Inhibitor-Induced Myocarditis

Abstract

: The improvement in tumor outcomes associated with the use of immune checkpoint inhibitors (ICIs) is supported by results of numerous clinical trials. Even though most publications reporting the clinical efficacy of these agents include a discussion of the biological mechanisms, narratives related to the complex nature of the adaptive immune response are frequently, though they should not be, mundane. It is also apparent that there tends to be a cursory, or even complete absence, of explanations related to the pathological mechanism(s) of the toxic reactions in the vast majority of papers that report adverse events associated with ICI therapy. Furthermore, the belief that cytotoxic CD8 + T cells mediate not only the antitumor, but also immune-related adverse, effects may be plausible, yet incorrect. This being the case, instead of providing only clinical details of a severe adverse event associated with combination ICI therapy in a patient with melanoma, the authors chose to scrutinize the repertoire and role of T cells in the pathogenesis of myocarditis as an example of other ICI-associated incidents of autoimmunity.