Zheng Yingxia, Han Li, Chen Zheyi, Li Yiyang, Zhou Bingqian, Hu Rui, Chen Shiyu, Xiao Haibo, Ma Yanhui, Xie Guohua, Yang Junyao, Ding Xianting, Shen Lisong
Department of Laboratory Medicine, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
State Key Laboratory of Oncogenes and Related Genes, School of Biomedical Engineering, Institute for Personalized Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
iScience. 2022 Jan 19;25(2):103785. doi: 10.1016/j.isci.2022.103785. eCollection 2022 Feb 18.
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-L1CD8 T cells were enriched in tumor lesions, spatially localized with PD-1CD8 T cells. Furthermore, PD-L1CD8 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-L1CD8 T cells development through STAT1/STAT3 signaling. Single-cell RNA sequencing data analysis further clarified PD-L1CD8 T cells elevated in the components related to downregulation of adaptive immune response. Collectively, our data demonstrated that PD-L1CD8 T cells enriched in lung cancer engaged in tolerogenic effects and may become a therapeutic target in lung cancer.
靶向检查点阻断以挽救T细胞免于耗竭的免疫疗法已成为治疗癌症的重要治疗策略。到目前为止，关于CD8 T细胞中PD-L1的图形模式和特征知之甚少。我们结合飞行时间细胞术（CyTOF）和成像质谱细胞术（IMC）方法分析原发性肺癌中的CD8 T细胞，发现PD-L1+CD8 T细胞在肿瘤病变中富集，与PD-1+CD8 T细胞在空间上定位在一起。此外，PD-L1+CD8 T细胞发挥调节功能，通过PD-L1/PD-1轴抑制CD8 T细胞的增殖和细胞毒性能力。此外，肿瘤来源的IL-27通过STAT1/STAT3信号促进PD-L1+CD8 T细胞的发育。单细胞RNA测序数据分析进一步阐明了与适应性免疫反应下调相关的成分中PD-L1+CD8 T细胞的增加。总体而言，我们的数据表明，在肺癌中富集的PD-L1+CD8 T细胞具有致耐受性作用，可能成为肺癌的治疗靶点。
