PD-1 Inhibitor Enhanced Radiosensitivity by Reactivating T Cells and Inducing G2/M Phase Arrest in Esophageal Squamous Cell Carcinoma
PD-1 Inhibitor Enhanced Radiosensitivity by Reactivating T Cells and Inducing G2/M Phase Arrest in Esophageal Squamous Cell Carcinoma
复制标题
PD-1 抑制剂通过重新激活 T 细胞并诱导食管鳞状细胞癌的 G2/M 期阻滞来增强放射敏感性
DOI：
10.1667/rade-22-00061.1
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发表时间：
2022-11-01
影响因子：
3.4
通讯作者：
Zhao, Kuaile
中科院分区：
文献类型：
--
作者：
Hao, Shengnan;Zhang, Xiangyan;Zhao, Kuaile
放射治疗是食管鳞癌的主要治疗手段，但放射抵抗最终导致治疗失败。放疗和PD-1抑制剂的组合显示出显著的抗肿瘤作用。我们的研究表明，在TCGA-ESCC队列中，高免疫评分、IFNG和CD8A水平与低放射敏感性指数（RSI）相关。阻断PD-1可促进耗竭T细胞增殖和IFN-c表达。PD-1转运蛋白再活化的T细胞以IFN-γ依赖性方式促进辐射抗性细胞中的G2/M期阻滞、凋亡和受损的DNA损伤。我们的研究表明PD-1抑制剂通过增强耗竭T细胞扩增和IFN-γ表达来提高放射敏感性，并强调新辅助抗PD-1治疗和放射治疗可以为改善癌症患者的结局提供最佳策略。(C)2022年，辐射研究协会。
Radiotherapy is a main treatment for esophageal squamous cell carcinoma (ESCC), but radioresistance leads to treatment failure ultimately. The combination of radiotherapy and PD-1 inhibitors showed significant antitumor effects. Our study showed that high-immune score, IFNG and CD8A level were associated with a low-radiosensitivity index (RSI) in the TCGA-ESCC cohort. And blocking PD-1 promoted exhausted T cells proliferation and IFN-c expression. PD-1 inhibitor-reactivated T cells promoted G2/M-phase arrest, apoptosis and impaired DNA damage in radioresistant cells in an IFN-gamma-dependent manner. Our study showed PD-1 inhibitors promote radiosensitivity though enhancing exhausted T cells expansion and IFN-gamma expression, and highlights that neoadjuvant anti-PD-1 therapy and radiotherapy could offer an optimum strategy for improving cancer patients' outcome. (C) 2022 by Radiation Research Society.