免疫检查点抑制剂与放疗相结合，可以增强放疗的免疫调节作用，减少远处未照射肿瘤的生长（远隔效应）；然而，结果仍然不太令人满意。因此，需要新的治疗方案来增强这种效果。我们之前的研究表明，双歧杆菌（Bi）与其特异性单克隆抗体（mAb）的组合可以靶向并缓解肿瘤部位的缺氧，并充当放射增敏剂。在本研究中，我们探讨了四联疗法（Bi  mAb 和 RT  αPD-1）的抗肿瘤功效。本研究还旨在探讨这一现象背后复杂的免疫机制。构建了4T1乳腺癌和CT26结肠癌肿瘤模型。通过肿瘤体积测量、生存分析、PET/CT成像、免疫细胞浸润分析和细胞因子表达水平，全面了解构建的四联疗法的影响。远隔效应在“冷”肿瘤模型中进一步放大，延长了生存期在荷瘤小鼠中。 Bi可以在原发性和继发性肿瘤中定植，并引导mAb到达肿瘤部位，激活补体，增强ADCC效应并启动先天免疫反应。然后与αPD-1和放疗结合，刺激适应性免疫反应，并与细胞因子协同作用，扩大免疫功效，产生有效的抗肿瘤免疫反应。Bi作为人工植入的厌氧靶点，在肿瘤处引起短暂的“感染” ，导致肿瘤局部发炎、“发热”，同时使用mAb靶向Bi，增强肿瘤的局部免疫效果，再结合放疗和αPD-1，放大远隔效应多个维度。因此，本研究为抗体靶向厌氧菌的多能免疫激活功能用于广泛转移癌症患者的RT治疗提供了新思路。© 2024。作者。

The combination of immune checkpoint inhibitors with radiotherapy can enhance the immunomodulation by RT and reduce the growth of distant unirradiated tumors (abscopal effect); however, the results are still not very satisfactory. Therefore, new treatment options are needed to enhance this effect. Our previous study showed that the combination of Bifidobacterium (Bi) and its specific monoclonal antibody (mAb) could target and alleviate hypoxia at the tumor site and act as a radiosensitizer. In this study, we explored the anti-tumor efficacy of quadruple therapy (Bi + mAb and RT + αPD-1). The current study also aimed to probe into the complex immune mechanisms underlying this phenomenon.Constructed 4T1 breast and CT26 colon cancer tumor models. A comprehensive picture of the impact of constructed quadruple therapy was provided by tumor volume measurements, survival analysis, PET/CT imaging, immune cell infiltration analysis and cytokine expression levels.The abscopal effect was further amplified in the "cold" tumor model and prolonged survival in tumor-bearing mice. Bi can colonized in primary and secondary tumors and direct the mAb to reach the tumor site, activate complement, enhance the ADCC effect and initiate the innate immune response. Then combined with αPD-1 and radiotherapy to stimulate adaptive immune response and synergize with cytokines to expand the immune efficacy and generate effective anti-tumor immune response.Bi was used as an artificially implanted anaerobic target to cause a transient "infection" at the tumor, causing the tumor to become locally inflamed and "hot", and at the same time, mAb was used to target Bi to enhance the local immune effect of the tumor, and then combined with radiotherapy and αPD-1 to amplify the abscopal effect in multiple dimensions. Therefore, the present study provided a new idea for the multipotent immune-activating function of antibody-targeted anaerobic bacteria for the RT treatment of extensively metastasized cancer patients.© 2024. The Author(s).