HAVCR2 and neoplasm: Several theories have been proposed to explain the unresponsiveness or evasion of ICIs, including intrinsic tumor modifications such as the lack of neoantigens, inactivation of the antigen presentation machinery, blocking of IFN-γ signaling, and extrinsic tumor modifications such as the loss of antigen-presenting cell function through the release of immunosuppressive cytokines, decreased T-cell proliferation and cytokine release, upregulation of additional ICs (e.g., TIM3 and LAG3), and activation of Tregs and MDSCs126,127.