癌症对免疫检查点抑制剂的耐药性促使人们研究利用放射治疗的免疫刺激特性来克服免疫逃避并改善治疗反应。然而，放射治疗-免疫治疗联合治疗的临床益处并不大。常规伴随肿瘤引流淋巴结照射（DLN IR）可能是罪魁祸首。 DLNs作为产生抗肿瘤免疫的关键位点，对于放射治疗的原位疫苗接种效果不可或缺。同时，由于转移扩散，DLN 保留通常是不可行的。使用雌性小鼠转移性疾病的鼠模型，我们证明延迟（辅助）DLN IR（而非新辅助）DLN IR 克服了伴随 DLN IR 对放射免疫治疗疗效的不利影响。此外，我们还发现 IR 诱导的 CCR7-CCL19/CCL21 归巢轴破坏是 DLN IR 产生有害影响的关键机制。我们的研究提出延迟 DLN IR 作为一种策略，以最大限度地提高放射免疫治疗在不同肿瘤类型和疾病阶段的疗效。© 2024。作者。

Cancer resistance to immune checkpoint inhibitors motivated investigations into leveraging the immunostimulatory properties of radiotherapy to overcome immune evasion and to improve treatment response. However, clinical benefits of radiotherapy-immunotherapy combinations have been modest. Routine concomitant tumor-draining lymph node irradiation (DLN IR) might be the culprit. As crucial sites for generating anti-tumor immunity, DLNs are indispensable for the in situ vaccination effect of radiotherapy. Simultaneously, DLN sparing is often not feasible due to metastatic spread. Using murine models of metastatic disease in female mice, here we demonstrate that delayed (adjuvant), but not neoadjuvant, DLN IR overcomes the detrimental effect of concomitant DLN IR on the efficacy of radio-immunotherapy. Moreover, we identify IR-induced disruption of the CCR7-CCL19/CCL21 homing axis as a key mechanism for the detrimental effect of DLN IR. Our study proposes delayed DLN IR as a strategy to maximize the efficacy of radio-immunotherapy across different tumor types and disease stages.© 2024. The Author(s).