Qu Zhifeng, Shi Linlin, Wang Pei, Zhao Anshun, Zheng Xuewei, Yin Qinan
Department 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.
Henan 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.
J Inflamm Res. 2025 Jul 12;18:9091-9106. doi: 10.2147/JIR.S531145. eCollection 2025.
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.
食管鳞状细胞癌（ESCC）的特征是慢性炎症、免疫逃逸和对放疗的抗性。诸如核因子-κB（NF-κB）、信号转导子和转录激活子3（STAT3）以及环氧合酶2（COX-2）等炎症通路会促进肿瘤进展并降低放射敏感性。放疗会激活促炎细胞因子并上调包括程序性死亡受体1（PD-1）和细胞毒性T淋巴细胞相关抗原4（CTLA-4）在内的免疫检查点，这会导致免疫抑制和治疗失败。对炎症和免疫检查点通路进行双重靶向已显示出逆转放射抗性和增强治疗反应的潜力。抑制COX-2可减轻炎症并改善肿瘤控制，而阻断PD-1可恢复T细胞功能并促进抗肿瘤免疫。整合抗炎成分、免疫检查点抑制剂（ICI）以及由分子谱分析指导的放疗的策略可能会改善ESCC的治疗效果。本综述聚焦于炎症介导的放射抗性的生物学基础，并提出双重靶向方法作为克服当前治疗局限性的有前景的选择。
