CXCR5+ monocyte emigration impairs the radiation-induced antitumor immune response
Year: 2026
Type: article
Abstract: A substantial portion of patients experience radioresistance, which impedes clinical benefit. The radiation-induced ‘protumor’ immune response is previously demonstrated to limit antitumor efficacy. However, the detailed mechanism remains to be explored. In this study, we observe CXCR5+ monocytes are enriched in tumor upon radiation. CXCR5 expression on monocytes in host is induced by tumor-derived VEGF through PI3K/mTOR/HIF-1α axis. Local radiation enhances CXCL13 expression from tumor cells, a specific ligand of CXCR5, which leads to the recruitment of CXCR5+ monocytes. Tumor-infiltrating CXCR5+ monocytes induce radioresistance by inhibiting CD8+ T cells through PD-1/PD-L1 interaction. Moreover, radiation-induced GM-CSF promotes the differentiation of CXCR5+ monocytes toward M2-like macrophages. In contrast, inhibiting VEGFR signaling, neutralizing CXCL13 and GM-CSF, or blocking PD-L1 facilitates radiation-induced tumor control by abrogating CXCR5+ monocyte-mediated immunosuppression. Furthermore, the CXCR5+ and CD14+ populations are increased in patients with cancer following radiotherapy. Monocyte is increased in the peripheral blood of patients with progressive disease following radiotherapy. These findings suggest potential strategies for blocking the CXCR5/CXCL13 axis to improve radiotherapy efficacy. The immune mechanism of radioresistance in cancer patients remains to be explored. The authors here show that CXCL13 is upregulated in tumor regions upon radiation, which recruits immune suppressive CXCR5+ monocytes. Blocking CXCR5/CXCL13 interactions facilitate tumor control following radiation.
Source: Nature Communications
Authors: Yutiantian Lei, Rui Jia, Chen Chen, Peihai Cao, Jiahong Shi, Mengdi Huang, Qiuyu Mu, Yixin Wang, Dairu Hou, Mingjun Si, Ruishan Guo, Jiahao Sun, Dingge Jiang, Yihan Wang, Tingting Lv, Ruiying Wang, Junyi Zhang, Du Yang, Hanmin Tang, Jianan Li, Liuyi Yang, Renyi Ding, Wenhua Li, Haiyan Liu, Anjun Jiao, Lingyun Hui, Yanxia Sui, Shan Huang, Mengjiao Cai, Chenchen He, Chen Lin, Fei Wang, Jinlu Ma, Suxia Han, Yuzhu Hou
Language: English
Topic: Immune cells in cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
OpenAlex ID: W7138870934