Pim2 negatively regulates T-cell immune responses through modulating autophagy

Abstract Pim kinases affect cell survival, proliferation, transcriptional activation, and protein translation by phosphorylating various target substrates. We previously showed that Pim2 plays a distinct role from Pim1 Pim3, negatively regulates T-cell allogeneic response anti-tumor immunity. was reported to promote the induction of autophagy in cancer cells, cellular process critically impacts effector function, survival memory formation. hypothesize constrains immune responses through modulating autophagy. Using western blot electron microscopy, we evaluated effect on autophagic flux resting activated T cells. deficiency cells attenuated LC3 lipidation, P62 degradation as well autophagosome formation, suggesting facilitates Mechanistically, directly bound with loss led accumulation which further blocked Furthermore, augmentation via overexpressing Atg5 or metformin treatment reduced cytokine production Pim2-deficient vitroand reversed heightened ability for inducing graft-versus-host disease controlling breast growth vivo. Taken together, is key promotor targeting suppress may represent promising strategy improve function immunotherapy. The work supported NIH grants: R01 CA258440 R21 CA263140.