Targeting Pim2 improves effector function and longevity of T cells in cancer immunotherapy

Abstract The Provirus Integration sites for Moloney murine leukemia virus (Pim) kinase family has been studied extensively in tumorigenesis. We previously reported a key role of Pim2 negatively regulating T-cell responses to alloantigen. further investigated how regulates mediated anti-tumor using models adoptive cell therapy (ACT) and autologous hematopoietic transplantation (HCT). found that −/−Pmel CD8 T cells showed enhanced ability controlling B16 melanoma growth following ACT. −/−T were more potent control C1498 after syngeneic HCT. Mechanistically, −/−CD8 exhibited increased effector cytokine production, metabolic activities, unexpectedly CD62L expression than WT controls activation. Activated had less apoptosis exhaustion during expansion IL-2. In vivo, differentiated into effector, but exhausted or suppressive subsets tumors. On the other hand, longevity spleen tumor draining lymph nodes. Our data indicates activity by their persistence secondary lymphoid organs function Blocking with Pim2-specific inhibitor improved graft-versus-leukemia HCT anti-melanoma effects inhibition also human melanoma-specific CD19 CAR-T cells. Taken together, targeting may serve as novel strategy improving cancer immunotherapy through enhancing differentiation NIH R01 CA258440 R21 CA263140 Xue-Zhong Yu, MCW Center Immunology Pilot Award Yongxia Wu