Although it has been reported that PD-1/PD-L1 ICIs exert their effects primarily within the TME, secondary lymphoid tissues, and tumor-draining lymph nodes (TdLNs) [103], the systemic nature of irAEs indicates that re-activated T cells also exert their effector functions elsewhere, evident by off-tumor toxicities in organs throughout the body. The gene discussed is CD274; the disease is neoplasm.