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.
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November 2022
RESEARCH ARTICLES|
August 22 2022
PD-1 Inhibitor Enhanced Radiosensitivity by Reactivating T Cells and Inducing G2/M Phase Arrest in Esophageal Squamous Cell Carcinoma
Shengnan Hao;
Shengnan Hao
1
a Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
b Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
c Shanghai Key Laboratory of Radiation Oncology, Shanghai 200032, China
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Xiangyan Zhang;
Xiangyan Zhang
1
d The Institute of Radiation Medicine, Fudan University, Shanghai 200032, China
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Litao Han;
Litao Han
e Department of Head and Neck Surgery, Fudan University Shanghai Cancer; Center, Fudan University, Shanghai 200032, China
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Xiangli Ma;
Xiangli Ma
d The Institute of Radiation Medicine, Fudan University, Shanghai 200032, China
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Yongzhan Nie;
Yongzhan Nie
f State Key Laboratory of Cancer Biology and Xijing Hospital of Digest Diseases, Fourth Military Medical University, Xi'an 710032, China
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Jiaying Deng;
Jiaying Deng
a Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
b Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
c Shanghai Key Laboratory of Radiation Oncology, Shanghai 200032, China
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Hongcheng Zhu;
Hongcheng Zhu
a Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
b Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
c Shanghai Key Laboratory of Radiation Oncology, Shanghai 200032, China
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Qi Liu;
Qi Liu
a Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
b Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
c Shanghai Key Laboratory of Radiation Oncology, Shanghai 200032, China
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Dashan Ai;
Dashan Ai
a Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
b Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
c Shanghai Key Laboratory of Radiation Oncology, Shanghai 200032, China
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Yun Chen;
Yun Chen
a Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
b Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
c Shanghai Key Laboratory of Radiation Oncology, Shanghai 200032, China
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Zhaolu Kong;
Zhaolu Kong
2
d The Institute of Radiation Medicine, Fudan University, Shanghai 200032, China
2 Corresponding authors: Kuaile Zhao, Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; email: kuaile_z@fudan.edu.cn; and Zhaolu Kong, The Institute of Radiation Medicine, Fudan University, Shanghai 200032, China; kongzhaolu@fudan.edu.cn.
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Kuaile Zhao
Kuaile Zhao
2
a Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China
b Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
c Shanghai Key Laboratory of Radiation Oncology, Shanghai 200032, China
2 Corresponding authors: Kuaile Zhao, Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China; email: kuaile_z@fudan.edu.cn; and Zhaolu Kong, The Institute of Radiation Medicine, Fudan University, Shanghai 200032, China; kongzhaolu@fudan.edu.cn.
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Radiat Res (2022) 198 (5): 458–466.
Article history
Received:
April 02 2022
Accepted:
July 18 2022
Citation
Shengnan Hao, Xiangyan Zhang, Litao Han, Xiangli Ma, Yongzhan Nie, Jiaying Deng, Hongcheng Zhu, Qi Liu, Dashan Ai, Yun Chen, Zhaolu Kong, Kuaile Zhao; PD-1 Inhibitor Enhanced Radiosensitivity by Reactivating T Cells and Inducing G2/M Phase Arrest in Esophageal Squamous Cell Carcinoma. Radiat Res 1 November 2022; 198 (5): 458–466. doi: https://doi.org/10.1667/RADE-22-00061.1
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