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The functional state of T cells is a key determinant for effective antitumor immunity and immunotherapy. Cellular metabolism, including lipid metabolism, controls T cell differentiation, survival, and effector functions. Here, we report that development of T cell senescence driven by both malignant tumor cells and regulatory T cells is a general feature in cancers. Senescent T cells have active glucose metabolism but exhibit unbalanced lipid metabolism. This unbalanced lipid metabolism results in changes of expression of lipid metabolic enzymes, which, in turn, alters lipid species and accumulation of lipid droplets in T cells. Tumor cells and Treg cells drove elevated expression of group IVA phospholipase A2, which, in turn, was responsible for the altered lipid metabolism and senescence induction observed in T cells. Mitogen-activated protein kinase signaling and signal transducer and activator of transcription signaling coordinately control lipid metabolism and group IVA phospholipase A2 activity in responder T cells during T cell senescence. Inhibition of group IVA phospholipase A2 reprogrammed effector T cell lipid metabolism, prevented T cell senescence in vitro, and enhanced antitumor immunity and immunotherapy efficacy in mouse models of melanoma and breast cancer in vivo. Together, these findings identify mechanistic links between T cell senescence and regulation of lipid metabolism in the tumor microenvironment and provide a new target for tumor immunotherapy.

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Femtosecond carrier dynamics in GaAs and Al0.3Ga0.7As are investigated using pump probe measurements of transient absorption saturation. Pulses of 35 fs duration are used both to excite carriers and to investigate their subsequent scattering out of their initial optically excited states. A two-component ultrafast relaxation is observed. In GaAs the initial rapid relaxation occurs on a time scale of 10–35 fs. Measurements performed in Al0.3Ga0.7As indicate that this initial process slows significantly to 130–170 fs for increasing band gap.