放射治疗通过促进单核细胞上PD-1的表达,削弱机体对肿瘤的免疫攻击能力,从而降低抗肿瘤免疫效果。
Radiotherapy drives PD-1 expression on monocytes to attenuate anti-tumor immunity
Zhang Jiandong, Chen Chen, Mu Qiuyu, Hou Yuzhu, Zhang Xiaozhi
Journal:CANCER IMMUNOLOGY IMMUNOTHERAPY
IF:5.8
DOI:10.1007/s00262-026-04519-4
PMID:
Published:2026-09-29
research field:肿瘤学辐射生物学肿瘤免疫学免疫治疗髓系细胞免疫检查点
Abstract
Radiotherapy is a cornerstone of cancer treatment, but resistance in solid tumors frequently leads to treatment failure. The mechanisms underlying radiotherapy-induced resistance, particularly its immunomodulatory effects, remain unclear. This study demonstrates that radiotherapy upregulates PD-1 expression on tumor-associated monocytes via the adenosine-A2AR-cAMP-PKA-NF-κB pathway. These PD-1 + monocytes suppress the anti-tumor activity of CD8 + T cells. Targeting this subset enhanced radiotherapy efficacy. Notably, tissues from radiotherapy-resistant patients showed elevated infiltration of PD-1 + monocytes. Thus, we identify a distinct immunosuppressive monocyte subset that accumulates post-radiotherapy. Its depletion represents a promising strategy to overcome resistance and boost anti-tumor immunity.
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