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PD-L1 on dendritic cells attenuates T cell activation and regulates response to immune checkpoint blockade
Nature Communications ( IF 16.6 ) Pub Date : 2020-09-24 , DOI: 10.1038/s41467-020-18570-x
Qi Peng 1, 2 , Xiangyan Qiu 3 , Zihan Zhang 1 , Silin Zhang 1 , Yuanyuan Zhang 1 , Yong Liang 3 , Jingya Guo 4 , Hua Peng 4 , Mingyi Chen 3 , Yang-Xin Fu 3 , Haidong Tang 1
Affiliation  

Immune checkpoint blockade therapies have shown clinical promise in a variety of cancers, but how tumor-infiltrating T cells are activated remains unclear. In this study, we explore the functions of PD-L1 on dendritic cells (DCs), which highly express PD-L1. We observe that PD-L1 on DC plays a critical role in limiting T cell responses. Type 1 conventional DCs are essential for PD-L1 blockade and they upregulate PD-L1 upon antigen uptake. Upregulation of PD-L1 on DC is mediated by type II interferon. While DCs are the major antigen presenting cells for cross-presenting tumor antigens to T cells, subsequent PD-L1 upregulation protects them from killing by cytotoxic T lymphocytes, yet dampens the antitumor responses. Blocking PD-L1 in established tumors promotes re-activation of tumor-infiltrating T cells for tumor control. Our study identifies a critical and dynamic role of PD-L1 on DC, which needs to be harnessed for better invigoration of antitumor immune responses.



中文翻译:

树突状细胞上的 PD-L1 减弱 T 细胞活化并调节对免疫检查点阻断的反应

免疫检查点阻断疗法已在多种癌症中显示出临床前景,但如何激活肿瘤浸润性 T 细胞仍不清楚。在这项研究中,我们探索了 PD-L1 对高度表达 PD-L1 的树突状细胞 (DC) 的功能。我们观察到 DC 上的 PD-L1 在限制 T 细胞反应方面起着关键作用。1 型常规 DC 对 PD-L1 阻断至关重要,它们在抗原摄取时上调 PD-L1。DC 上 PD-L1 的上调是由 II 型干扰素介导的。虽然 DC 是将肿瘤抗原交叉呈递给 T 细胞的主要抗原呈递细胞,但随后的 PD-L1 上调可保护它们免受细胞毒性 T 淋巴细胞的杀伤,同时抑制抗肿瘤反应。在已建立的肿瘤中阻断 PD-L1 可促进肿瘤浸润性 T 细胞的重新激活以控制肿瘤。

更新日期:2020-09-24
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