Conditional deletion of SHP2 in T cells with CD4-Cre (Ptpn11fl/fl; CD4-Cre) is providing evidence that SHP2 is not required for T cell exhaustion: Ptpn11-deficient mice in chronic viral infection or cancer/melanoma challenge did not display differing expressions of T cell exhaustion marker expressions and responses to anti-PD-1 treatment as compared to the wild-type or externally wild-type mice, suggesting that alternative phosphatases (e.g., SHP1) can mediate inhibitive signals in vivo [58]. This evidence concerns the gene PDCD1 and cancer.