This has lead to re-evaluations of the significance of iR as “exhaustion markers”, for instance, in the context of SIV infection [where PD1 expression was associated with a CCR7− CCR5+ phenotype rather than dysfunction per se, questioning the value of PD1 as a marker of “immune exhaustion” (93)], as well as in cancer [where BTLA and PD1 are proposed to mark cells in a “heightened state of T cell activation” (94)]. This evidence concerns the gene PDCD1 and cancer.