Over the last decade, several studies have further linked expression of iRs (e.g. PD1, CTLA-4, TIM3, LAG3, CD160, BTLA, and 2B4) to the phenomenon of “T cell exhaustion” both in mouse models and in patients, in chronic infections, including HIV, hepatitis C virus, EBV, malaria, as well as autoimmune disorders such as systemic lupus erythematosus and in several cancers (41–50). The gene discussed is IARS1; the disease is cancer.