LAUSR

Significance Cancers and chronic infectious pathogens often evade immune-mediated elimination by suppressing T cell function via engaging inhibitory receptors expressed on T cells. The phospholipid lysophosphatidic acid (LPA) is often increased systemically from basal concentrations upon development of cancer and chronic infections. We previously showed that, at these elevated concentrations, LPA suppresses the ability of CD8 T cells to kill malignant cells and to control tumor growth. Here, we demonstrate that LPA signaling suppresses T cell function via disrupting T cell receptor–induced cytoskeletal dynamics, immune synapse formation, signal transduction, and the tubulin code. This report identifies a targetable mechanism of receptor-mediated inhibition of T cell function that could be used in combination therapies to enhance antitumor and antiviral immunity.