细胞内在的 PD-L1 缺失维持效应 CD8(+) T 细胞反应并促进抗肿瘤 T 细胞治疗

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 (PD-1) 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.