Lang Yanyan, Huang Hao, Jiang Hongwei, Wu Shaoxian, Fang Zhang, Zhang Dachuan, Qian Heya, Liu Yingting, Yuan Maoling, Xu Bin, Chen Lujun, Zheng Xiao, Jiang Jingting
Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Jiangsu, 213003, Changzhou, China.
Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Jiangsu, 213003, Changzhou, China.
Cancer Immunol Immunother. 2025 Aug 6;74(9):284. doi: 10.1007/s00262-025-04138-5.
Colorectal cancer (CRC) continues to be a major global health challenge due to its high incidence and mortality rates, emphasizing the critical need for innovative therapeutic strategies. IL-1R2, a member of the IL-1 receptor family, plays a pivotal role in both tumorigenesis and antitumor immunity. However, its precise role in tumor development and its impact on immune checkpoint inhibitors (ICIs) therapy in CRC remain poorly understood. We examined tumor progression in wild-type and IL-1R2-deficient mice using an AOM/DSS-induced colitis-associated colorectal cancer model treated with combined ICIs therapy. Our findings revealed that IL-1R2 deficient mice exhibited a significant reduction in tumor burden, accompanied by alterations in the carcinogenic program and enhanced immunogenicity of tumor cells. Furthermore, the deletion of IL-1R2 resulted in an increased proportion of exhausted CD8 T cells, a population commonly enriched for tumor antigen-specific T cells, suggesting an augmentation of tumor-specific immune responses. Moreover, IL-1R2 deletion upregulated genes linked to antigen presentation in dendritic cells, indicating enhanced activation of the adaptive immune system. Collectively, these findings position IL-1R2 as a promising therapeutic target for improving the efficacy of treatment strategies in CRC.
由于结直肠癌（CRC）的高发病率和死亡率，它仍然是一个重大的全球健康挑战，这凸显了对创新治疗策略的迫切需求。白细胞介素-1受体2（IL-1R2）是白细胞介素-1受体家族的成员，在肿瘤发生和抗肿瘤免疫中都起着关键作用。然而，其在肿瘤发展中的精确作用及其对CRC中免疫检查点抑制剂（ICIs）治疗的影响仍知之甚少。我们使用联合ICIs治疗的AOM/DSS诱导的结肠炎相关结直肠癌模型，研究了野生型和IL-1R2缺陷型小鼠的肿瘤进展。我们的研究结果表明，IL-1R2缺陷型小鼠的肿瘤负担显著降低，同时致癌程序发生改变，肿瘤细胞的免疫原性增强。此外，IL-1R2的缺失导致耗竭的CD8 T细胞比例增加，这一群体通常富含肿瘤抗原特异性T细胞，表明肿瘤特异性免疫反应增强。此外，IL-1R2的缺失上调了与树突状细胞中抗原呈递相关的基因，表明适应性免疫系统的激活增强。总的来说，这些发现表明IL-1R2是提高CRC治疗策略疗效的一个有前景的治疗靶点。
