On March 19, Han Suxia &Ma Jinlu’s team from the Department of Radiation Oncology of the First Affiliated Hospital (FAH) of Xi’an Jiaotong University (XJTU), in collaboration with Hou Yuzhu’s team from the School of Basic Medical Sciences, published their findings on the immunology of radiotherapy resistance, entitled “CXCR5+ monocyte emigration impairs the radiation-induced antitumor immune response”, in Nature Communications. The study, for the first time, identifies the pivotal role of CXCR5+ monocytes in radiotherapy resistance, providing new theory and strategies for combined radiotherapy-immunotherapy in cancer treatment.
Radiotherapy is a core cancer treatment modality, but the immune responses it induces are bidirectional; the radiation-induced ‘protumor’ immune responses is previously demonstrated to limit antitumor efficacy, making the investigation of its mechanisms crucial for developing combination treatment strategies.
This study found that CXCR5+ monocytes inhibit radiotherapy-mediated antitumor immune responses. Tumor-derived VEGF induces CXCR5 expression in bone marrow monocytes, while irradiation promotes tumor cells to produce the ligand CXCL13, thereby recruiting CXCR5+ monocytes to infiltrate irradiated tumor tissues. These cells exhibit high expression of PD-L1, which suppresses CD8+ T cell function, and can also differentiate into suppressive macrophages under the induction of GM-CSF, thereby diminishing the efficacy of radiotherapy through dual mechanisms. Clinical detection further confirmed a significant increase in the proportion of CXCR5+ monocytes in the peripheral blood of patients with progressive disease following radiotherapy.
This study also confirmed that during radiotherapy, the combined blockade of the CXCR5-CXCL13 axis, inhibition of PD-1/PD-L1 signaling, and neutralization of GM-CSF can effectively enhance radiotherapy efficacy, providing a new avenue for optimizing comprehensive tumor treatment strategies and improving patient outcomes.
Original link: https://www.nature.com/articles/s41467-026-70858-6
