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

doi:10.1016/j.isci.2022.103785

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

iScience. 2022 Jan 19;25(2):103785. doi: 10.1016/j.isci.2022.103785. eCollection 2022 Feb 18.

Authors

Yingxia Zheng¹, Li Han¹, Zheyi Chen¹, Yiyang Li², Bingqian Zhou¹, Rui Hu³, Shiyu Chen¹, Haibo Xiao³, Yanhui Ma¹, Guohua Xie¹, Junyao Yang¹, Xianting Ding², Lisong Shen^{1

4

5}

Affiliations

¹ Department of Laboratory Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
² State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
³ Department of Thoracic Surgery, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200230, China.
⁴ Faculty of Medical Laboratory Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
⁵ Xin Hua Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.

Abstract

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.

Keywords: Biological sciences; Immune system; Transcriptomics.