HAVCR2 and neoplasm: T-cell exhaustion is a status of dysfunction and hyporesponse, which manifests as impaired anti-tumor ability, reduced cytotoxicity and effector cytokine release, such as GranzymeB and IFN-γ, attenuated proliferation potential, and persistent expression of checkpoint molecules like programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), T-cell immunoglobulin domain and mucin domain-3 (TIM3), and lymphocyte-activation gene 3 (LAG3) [56].