PD-L1+CD8+ T cells enrichment in lung cancer exerted regulatory function and tumor-promoting tolerance
Yingxia Zheng,
Li Han,
Zheyi Chen,
Yiyang Li,
Bingqian Zhou,
Rui Hu,
Shiyu Chen,
Haibo Xiao,
Yanhui Ma,
Guohua Xie,
Junyao Yang,
Xianting Ding,
Lisong Shen
Affiliations
Yingxia Zheng
Department of Laboratory Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Corresponding author
Li Han
Department of Laboratory Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Zheyi Chen
Department of Laboratory Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Yiyang Li
State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200092, China
Bingqian Zhou
Department of Laboratory Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Rui Hu
Department of Thoracic Surgery, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200230, China
Shiyu Chen
Department of Laboratory Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Haibo Xiao
Department of Thoracic Surgery, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200230, China
Yanhui Ma
Department of Laboratory Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Guohua Xie
Department of Laboratory Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Junyao Yang
Department of Laboratory Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China
Xianting Ding
State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200092, China; Corresponding author
Lisong Shen
Department of Laboratory Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Faculty of Medical Laboratory Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Xin Hua Children’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China; Corresponding author
Summary: 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.
