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RNAseq analysis of immune-related genes shows commonality in autoimmune and ICI-induced colitis

• Immune checkpoint inhibitors (ICIs) have made a profound impact on the treatment of a variety of cancers. However, toxicities can occur that cause significant morbidity and/or mortality• CIs can cause unique autoimmune toxicities, resulting in inflammation of numerous organ systems, in some cases fatal. The molecular underpinnings of these toxicities have not been extensively explored.• We recently reported a small case series of two patients with myocarditis resulting in death arising following combination ICI therapy (Johnson et al, NEJM, 2016).• High lymphocytic infiltration, coupled with PD-L1 expression was present in the affected myocardium and skeletal muscle. Common T cell clones were identified between the affected tissue and tumor, and abnormal expression of muscle-specific transcripts was identified in the associated tumor, suggesting release of peripheral tolerance to tumor-expressed self-antigens.