TIM-3+PD-1+ TILs have been identified in murine models of colon adenocarcinoma, breast adenocarcinoma, and melanoma; coexpression of these two T cell “exhaustion” markers has been shown to be the most functionally impaired group of CD8+ TIL populations as determined by lowest IL2, TNF and IFNγ production and progression through the cell cycle [90, 91]. This evidence concerns the gene PDCD1 and melanoma.