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22 August 2022 PD-1 Inhibitor Enhanced Radiosensitivity by Reactivating T Cells and Inducing G2/M Phase Arrest in Esophageal Squamous Cell Carcinoma
Shengnan Hao, Xiangyan Zhang, Litao Han, Xiangli Ma, Yongzhan Nie, Jiaying Deng, Hongcheng Zhu, Qi Liu, Dashan Ai, Yun Chen, Zhaolu Kong, Kuaile Zhao
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Abstract

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-γ expression. PD-1 inhibitor-reactivated T cells promoted G2/M-phase arrest, apoptosis and impaired DNA damage in radioresistant cells in an IFN-γ-dependent manner. Our study showed PD-1 inhibitors promote radiosensitivity though enhancing exhausted T cells expansion and IFN-γ expression, and highlights that neoadjuvant anti-PD-1 therapy and radiotherapy could offer an optimum strategy for improving cancer patients' outcome.

©2022 by Radiation Research Society. All rights of reproduction in any form reserved.
Shengnan Hao, Xiangyan Zhang, Litao Han, Xiangli Ma, Yongzhan Nie, Jiaying Deng, Hongcheng Zhu, Qi Liu, Dashan Ai, Yun Chen, Zhaolu Kong, and Kuaile Zhao "PD-1 Inhibitor Enhanced Radiosensitivity by Reactivating T Cells and Inducing G2/M Phase Arrest in Esophageal Squamous Cell Carcinoma," Radiation Research 198(5), 458-466, (22 August 2022). https://doi.org/10.1667/RADE-22-00061.1
Received: 2 April 2022; Accepted: 18 July 2022; Published: 22 August 2022
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