Shi Weiwei, Yang Bo, Sun Qiong, Meng Jing, Zhao Xiao, Du Sicheng, Li Xiaoyan, Jiao Shunchang
Department of Oncology, PLA General Hospital, Beijing, China.
Department of Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Int Immunopharmacol. 2020 Feb 19;82:106295. doi: 10.1016/j.intimp.2020.106295.
PD-1 inhibitors have been used to revive exhausted T cell responses in non-small cell lung cancer (NSCLC) and other malignancies. CXCR5 T follicular helper (Tfh) cells are characterized by constitutive high PD-1 expression and have been associated with the formation of tertiary lymphoid structures and implicated in antitumor immunity. In this study, we investigated the effect of PD-1 and PD-1 inhibition on CXCR5 CD4 T cells. Data showed that CXCR5 CD4 T cells in both healthy subjects and NSCLC patients presented markedly higher PD-1 expression than CXCR5 CD4 T cells. Both CXCR5 and CXCR5 CD4 T cells from NSCLC patients presented higher PD-1 expression than their counterparts in healthy subjects. PD-1 CXCR5 CD4 T cells were functional, could express IL-21, IL-10, and CXCL13 upon stimulation, demonstrated auxiliary effects toward CD8 T cell-mediated IFN-γ production and proliferation, and promoted IgM and IgG production. However, the potency of PD-1 CXCR5 CD4 T cells was lower than the potency of PD-1 CXCR5 CD4 T cells. PD-1 blocking could significantly enhance the effector functions of PD-1 CXCR5 CD4 T cells. Overall, this study demonstrated that PD-1 CXCR5 CD4 T cells could promote CD8 T cell and B cell inflammation and could be modulated by PD-1 inhibition.
程序性死亡受体1（PD-1）抑制剂已被用于恢复非小细胞肺癌（NSCLC）和其他恶性肿瘤中耗竭的T细胞反应。CXCR5滤泡辅助性T（Tfh）细胞的特征是组成性高表达PD-1，并与三级淋巴结构的形成相关，且参与抗肿瘤免疫。在本研究中，我们调查了PD-1及其抑制对CXCR5 CD4 T细胞的影响。数据显示，健康受试者和NSCLC患者的CXCR5 CD4 T细胞的PD-1表达均明显高于CXCR5 CD4 T细胞。NSCLC患者的CXCR5和CXCR5 CD4 T细胞的PD-1表达均高于健康受试者中的对应细胞。PD-1 CXCR5 CD4 T细胞具有功能，在受到刺激时可表达白细胞介素-21（IL-21）、白细胞介素-10（IL-10）和CXC趋化因子配体13（CXCL13），对CD8 T细胞介导的干扰素-γ（IFN-γ）产生和增殖具有辅助作用，并促进免疫球蛋白M（IgM）和免疫球蛋白G（IgG）的产生。然而，PD-1 CXCR5 CD4 T细胞的效能低于PD-1 CXCR5 CD4 T细胞。阻断PD-1可显著增强PD-1 CXCR5 CD4 T细胞的效应功能。总体而言，本研究表明，PD-1 CXCR5 CD4 T细胞可促进CD8 T细胞和B细胞炎症，且可通过抑制PD-1进行调节。
