In addition, treatment-related factors, such as the type of ICI (anti-PD-1 versus anti-CTLA4), combination of ICIs, as well as intrinsic factors including tumor and genetic heterogeneities, cancer type, tumour microenvironment and the microbiota might also influence the development of autoimmune irAEs (12, 32, 33). The gene discussed is CTLA4; the disease is cancer.