We chose to focus on these coinhibitory receptors because (a) they were both differentially expressed between Tr1 and Th1 cells (Figure 1C), (b) LAG3 has a strong association with Tr1 cells and their functions (14), and (c) TIM3 loss-of-function mutations are associated with human diseases and it has emerged as an important target for immune checkpoint blockade in trials to treat several different human cancers (28). This evidence concerns the gene HAVCR2 and cancer.