Cell-intrinsic PD-L1 ablation sustains effector CD8+T cell responses and promotes antitumor T cell therapy

Adoptive cell therapies are emerging forms of immunotherapy that reprogram T cells for enhanced antitumor responses. Although surface programmed cell death-ligand 1 (PD-L1)/programmed cell death protein 1 (PD1) engagement inhibits antitumor immunity, the role of cell -intrinsic PD -L1 in adoptive T cell therapy remains unknown. Here, we found that intracellular PD -L1 was enriched in tumor -infiltrating CD8+ T cells of cancer patients. PD -L1 ablation promoted antitumor immune responses and the maintenance of an effector -like state of therapeutic CD8+ T cells, while blockade of surface PD -L1 was unable to impact on their expansion and function. Moreover, cell -intrinsic PD -L1 impeded CD8+ T cell activity, which partially relied on mTORC1 signaling. Furthermore, endogenous tumor -reactive CD8+ T cells were motivated by BATF3-driven dendritic cells after adoptive transfer of PD -L1 -deficient therapeutic CD8+ T cells. This role of cell -intrinsic PD -L1 in therapeutic CD8+ T cell dysfunction highlights that disrupting cell -intrinsic PD -L1 in CD8+ T cells represents a viable approach to improving T cell -based cancer immunotherapy.