GPR65 and neoplasm: Interestingly, GPR65 was additionally identified to be part of the co-inhibitory receptor module driven by IL-27.123 In future studies, additional genes that are shared between proinflammatory Th1 and Th17 signatures and the exhausted T-cell signature may provide a novel set of targets that might differentially impact generation of pathogenic Th17 cells and thereby impact autoimmunity but at the same time may affect development of T-cell exhaustion and promote anti-tumor immunity (Fig. 4).