HAVCR2 and neoplasm: Exhausted T cells, which arise in response to chronic antigen exposure in the tumor microenvironment, exhibit progressive loss of effector function, sustained expression of multiple inhibitory receptors such as PD1, cytotoxic T lymphocyte antigen 4 (CTLA-4), T-cell immunoglobulin domain and mucin domain protein 3 (TIM-3).