PD-L1+CD8+ T cells enrichment in lung cancer exerted regulatory function and tumor-promoting tolerance

Immunotherapy targeting checkpoint blockade to rescue T cells from exhaustion has become an essential therapeutic strategy in treating cancers. Till now, little is known about the PD-L1 graphic pattern and characteristics in CD8(+) T cells. We combined cytometry by time-of-flight (CyTOF) and imaging mass cytometry (IMC) approaches to analyze CD8(+) T cells from primary lung cancers and discovered that PD-L1(+)CD8(+) T cells were enriched in tumor lesions, spatially localized with PD-1+CD8(+) T cells. Furthermore, PD-L1(+)CD8(+) T cells exerted regulatory functions that inhibited CD8(+) T cells proliferation and cytotoxic abilities through the PD-L1/PD-1 axis. Moreover, tumor-derived IL-27 promotes PD-L1(+)CD8(+) T cells development through STAT1/STAT3 signaling. Single-cell RNA sequencing data analysis further clarified PD-L1(+)CD8(+) T cells elevated in the components related to downregulation of adaptive immune response. Collectively, our data demonstrated that PD-L1(+)CD8(+) T cells enriched in lung cancer engaged in tolerogenic effects and may become a therapeutic target in lung cancer.

Automated summary

We discovered an enrichment of PD-L1(+)CD8(+) T cells in lung cancer, which were spatially localized with PD-1(+)CD8(+) T cells. These PD-L1(+)CD8(+) T cells exhibited regulatory functions that inhibited the proliferation and cytotoxic abilities of other CD8(+) T cells through the PD-L1/PD-1 axis. Tumor-derived IL-27 was found to promote the development of PD-L1(+)CD8(+) T cells through STAT1/STAT3 signaling, leading to downregulation of the adaptive immune response.