ENPP2 and neoplasm: These data not only add to the existing body of evidence that LPA and ATX play an important role in tumor progression, but also provide convincing evidence that lipid signaling could be exploited as an approach to (1) prevent and/or reinvigorate dysfunctional CD8 T cells, (2) promote effective endogenous anti-tumor immunity, and (3) improve clinical responses to immunotherapy.