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.