当前位置: X-MOL 学术Cancer Cell › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Tumor-Repopulating Cells Induce PD-1 Expression in CD8+ T Cells by Transferring Kynurenine and AhR Activation.
Cancer Cell ( IF 48.8 ) Pub Date : 2018-03-12 , DOI: 10.1016/j.ccell.2018.02.005
Yuying Liu , Xiaoyu Liang , Wenqian Dong , Yi Fang , Jiadi Lv , Tianzhen Zhang , Roland Fiskesund , Jing Xie , Jinyan Liu , Xiaonan Yin , Xun Jin , Degao Chen , Ke Tang , Jingwei Ma , Huafeng Zhang , Jing Yu , Jun Yan , Huaping Liang , Siqi Mo , Feiran Cheng , Yabo Zhou , Haizeng Zhang , Jing Wang , Jingnan Li , Yang Chen , Bing Cui , Zhuo-Wei Hu , Xuetao Cao , F. Xiao-Feng Qin , Bo Huang

Despite the clinical successes fostered by immune checkpoint inhibitors, mechanisms underlying PD-1 upregulation in tumor-infiltrating T cells remain an enigma. Here, we show that tumor-repopulating cells (TRCs) drive PD-1 upregulation in CD8+ T cells through a transcellular kynurenine (Kyn)-aryl hydrocarbon receptor (AhR) pathway. Interferon-γ produced by CD8+ T cells stimulates release of high levels of Kyn produced by TRCs, which is transferred into adjacent CD8+ T cells via the transporters SLC7A8 and PAT4. Kyn induces and activates AhR and thereby upregulates PD-1 expression. This Kyn-AhR pathway is confirmed in both tumor-bearing mice and cancer patients and its blockade enhances antitumor adoptive T cell therapy efficacy. Thus, we uncovered a mechanism of PD-1 upregulation with potential tumor immunotherapeutic applications.

中文翻译:

肿瘤繁殖细胞通过转移Kynurenine和AhR激活而诱导CD8 + T细胞中PD-1表达。

尽管免疫检查点抑制剂促进了临床成功,但肿瘤浸润性T细胞中PD-1上调的潜在机制仍是一个谜。在这里,我们显示肿瘤繁殖细胞(TRCs)通过跨细胞的犬尿氨酸(Kyn)-芳烃受体(AhR)途径驱动CD8 + T细胞中PD-1的上调。CD8 + T细胞产生的干扰素-γ刺激TRC产生的高水平Kyn释放,并被转移到相邻的CD8 +T细胞通过转运蛋白SLC7A8和PAT4。Kyn诱导并激活AhR,从而上调PD-1表达。此Kyn-AhR途径在荷瘤小鼠和癌症患者中均得到证实,其阻断作用增强了抗肿瘤过继T细胞疗法的疗效。因此,我们发现了PD-1上调与潜在的肿瘤免疫治疗应用的机制。
更新日期:2018-03-13
down
wechat
bug