Dual Targeting of Inflammatory and Immune Checkpoint Pathways to Overcome Radiotherapy Resistance in Esophageal Squamous Cell Carcinoma
Zhifeng Qu,1 Linlin Shi,2 Pei Wang,1 Anshun Zhao,2 Xuewei Zheng,3 Qinan Yin1,3 1Department of Radiation Oncology; Cancer Institute, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, People’s Republic of China; 2Henan Key Laborator...
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Dove Medical Press
2025-07-01
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| author | Qu Z Shi L Wang P Zhao A Zheng X Yin Q |
| author_facet | Qu Z Shi L Wang P Zhao A Zheng X Yin Q |
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| description | Zhifeng Qu,1 Linlin Shi,2 Pei Wang,1 Anshun Zhao,2 Xuewei Zheng,3 Qinan Yin1,3 1Department of Radiation Oncology; Cancer Institute, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, People’s Republic of China; 2Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment; Henan Key Laboratory of Cancer Epigenetics; College of Basic Medicine and Forensic Medicine, Cancer Hospital, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, People’s Republic of China; 3Precision Medicine Laboratory, School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, People’s Republic of ChinaCorrespondence: Qinan Yin, Department of Radiation Oncology; Cancer Institute, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, No. 636, Guanlin Avenue, Luoyang, 471003, People’s Republic of China, Email qinanyin@haust.edu.cn Xuewei Zheng Precision Medicine Laboratory, School of Medical Technology and Engineering, Henan University of Science and Technology, No. 263, Kaiyuan Avenue, Luoyang, 471000, People’s Republic of China, Email xwzheng0529@163.comAbstract: Esophageal squamous cell carcinoma (ESCC) is characterized by chronic inflammation, immune evasion, and resistance to RT. Inflammatory pathways such as nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3), and cyclooxygenase 2 (COX-2) promote tumor progression and reduce radiosensitivity. RT activates pro-inflammatory cytokines and upregulates immune checkpoints including programmed death 1 (PD-1) and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), which contribute to immune suppression and treatment failure. Dual targeting of inflammatory and immune checkpoint pathways has shown potential to reverse radio resistance and enhance therapeutic response. Inhibition of COX-2 can reduce inflammation and improve tumor control, while blockade of PD-1 can restore T cell function and promote antitumor immunity. Strategies that integrate anti-inflammatory components, immune checkpoint inhibitors (ICIs), and RT guided by molecular profiling may improve treatment outcomes in ESCC. This review focuses on the biological basis of inflammation-mediated radio resistance and presents dual targeting approaches as promising options to overcome current therapeutic limitations.Keywords: esophageal squamous cell carcinoma, inflammation, radiotherapy (RT) resistance |
| format | Article |
| id | doaj-art-b8b43d2bf3334d97bfbf977ce3e0f63d |
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| publishDate | 2025-07-01 |
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| spelling | doaj-art-b8b43d2bf3334d97bfbf977ce3e0f63d2025-07-13T18:21:55ZengDove Medical PressJournal of Inflammation Research1178-70312025-07-01Volume 18Issue 190919106104749Dual Targeting of Inflammatory and Immune Checkpoint Pathways to Overcome Radiotherapy Resistance in Esophageal Squamous Cell CarcinomaQu Z0Shi L1Wang P2Zhao AZheng X3Yin Q4Department of Radiation OncologyCollege of Clinical MedicineDepartment of Radiation OncologySchool of Medical Technology and EngineeringDepartment of Radiation OncologyZhifeng Qu,1 Linlin Shi,2 Pei Wang,1 Anshun Zhao,2 Xuewei Zheng,3 Qinan Yin1,3 1Department of Radiation Oncology; Cancer Institute, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, People’s Republic of China; 2Henan Key Laboratory of Microbiome and Esophageal Cancer Prevention and Treatment; Henan Key Laboratory of Cancer Epigenetics; College of Basic Medicine and Forensic Medicine, Cancer Hospital, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, People’s Republic of China; 3Precision Medicine Laboratory, School of Medical Technology and Engineering, Henan University of Science and Technology, Luoyang, People’s Republic of ChinaCorrespondence: Qinan Yin, Department of Radiation Oncology; Cancer Institute, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, No. 636, Guanlin Avenue, Luoyang, 471003, People’s Republic of China, Email qinanyin@haust.edu.cn Xuewei Zheng Precision Medicine Laboratory, School of Medical Technology and Engineering, Henan University of Science and Technology, No. 263, Kaiyuan Avenue, Luoyang, 471000, People’s Republic of China, Email xwzheng0529@163.comAbstract: Esophageal squamous cell carcinoma (ESCC) is characterized by chronic inflammation, immune evasion, and resistance to RT. Inflammatory pathways such as nuclear factor-kappa B (NF-κB) and signal transducer and activator of transcription 3 (STAT3), and cyclooxygenase 2 (COX-2) promote tumor progression and reduce radiosensitivity. RT activates pro-inflammatory cytokines and upregulates immune checkpoints including programmed death 1 (PD-1) and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), which contribute to immune suppression and treatment failure. Dual targeting of inflammatory and immune checkpoint pathways has shown potential to reverse radio resistance and enhance therapeutic response. Inhibition of COX-2 can reduce inflammation and improve tumor control, while blockade of PD-1 can restore T cell function and promote antitumor immunity. Strategies that integrate anti-inflammatory components, immune checkpoint inhibitors (ICIs), and RT guided by molecular profiling may improve treatment outcomes in ESCC. This review focuses on the biological basis of inflammation-mediated radio resistance and presents dual targeting approaches as promising options to overcome current therapeutic limitations.Keywords: esophageal squamous cell carcinoma, inflammation, radiotherapy (RT) resistancehttps://www.dovepress.com/dual-targeting-of-inflammatory-and-immune-checkpoint-pathways-to-overc-peer-reviewed-fulltext-article-JIREsophageal squamous cell carcinomaInflammationRadiotherapy (RT) resistance |
| spellingShingle | Qu Z Shi L Wang P Zhao A Zheng X Yin Q Dual Targeting of Inflammatory and Immune Checkpoint Pathways to Overcome Radiotherapy Resistance in Esophageal Squamous Cell Carcinoma Journal of Inflammation Research Esophageal squamous cell carcinoma Inflammation Radiotherapy (RT) resistance |
| title | Dual Targeting of Inflammatory and Immune Checkpoint Pathways to Overcome Radiotherapy Resistance in Esophageal Squamous Cell Carcinoma |
| title_full | Dual Targeting of Inflammatory and Immune Checkpoint Pathways to Overcome Radiotherapy Resistance in Esophageal Squamous Cell Carcinoma |
| title_fullStr | Dual Targeting of Inflammatory and Immune Checkpoint Pathways to Overcome Radiotherapy Resistance in Esophageal Squamous Cell Carcinoma |
| title_full_unstemmed | Dual Targeting of Inflammatory and Immune Checkpoint Pathways to Overcome Radiotherapy Resistance in Esophageal Squamous Cell Carcinoma |
| title_short | Dual Targeting of Inflammatory and Immune Checkpoint Pathways to Overcome Radiotherapy Resistance in Esophageal Squamous Cell Carcinoma |
| title_sort | dual targeting of inflammatory and immune checkpoint pathways to overcome radiotherapy resistance in esophageal squamous cell carcinoma |
| topic | Esophageal squamous cell carcinoma Inflammation Radiotherapy (RT) resistance |
| url | https://www.dovepress.com/dual-targeting-of-inflammatory-and-immune-checkpoint-pathways-to-overc-peer-reviewed-fulltext-article-JIR |
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