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

Targeting checkpoint blockade to rescue exhausted regulatory T cells (Tregs) has become an essential immunotherapy strategy in treating cancer. Until now, the CD4+ Tregs and PD-1+CD8+ T cells were demonstrated to reduce immunogenic responses. In contrast, little is known about the PD-L1 graphic pattern and characteristics in CD8+ T cells. We performed two high-throughput analysis approaches on tumor-infiltrating CD8+ T cells in lung cancers. We discovered PD-L1+CD8+ T cells enriched in tumor lesions, localized with PD-1+CD8+ affected T cells, and owned regulatory functions. Moreover, tumor-derived IL-27 promoted the development of PD-L1+CD8+ T cells through STAT1/STAT3 signaling. Single-cell RNA sequencing data analysis further clarified the enrichment of PD-L1+CD8+ T cells related to the downregulation of adaptive immune response. Additionally, enrichment of this subset was correlated with poor survival of lung cancer patients. Our data collectively demonstrated that PD-L1+CD8+ T cells potentially become a prognostic biomarker in lung cancer. Overall design: CD8 T cells were stimulated with IL-27 for 48 hours, CD8+PD-L1+ and CD8+PD-L1- T cells were sorted into tubes containing lysis buffer, and transcriptome amplifications were performed following the Smart-Seq2 protocol.