HAVCR2 and neoplasm: Interestingly, in preclinical models, TIM-3+/PD-1+ tumor-infiltrating lymphocytes (TILs) are characterized by significantly impaired proliferation and reduced cytokine production (IL-2, tumor necrosis factor [TNF], and IFN-γ) with a more severe exhausted phenotype than TIM-3−/PD-1+ TILs [45].