Patients with breast cancer obtain limited clinical benefits from immune checkpoint inhibitors (ICIs), pointing to the existence of multiple immunological alterations that cannot be simultaneously normalized with immunotherapy. Accumulating preclinical evidence suggests that radiation therapy (RT) can be harnessed to sensitize primary and metastatic mouse mammary carcinomas to ICIs. However, various clinical trials combining RT with ICIs in patients with breast cancer documented little cooperativity. Here, we discuss immunological barriers that may prevent RT from unlocking the therapeutic potential of ICIs in patients with breast cancer. These observations may inspire the development of combinatorial regimens that might benefit patients with diverse neoplastic conditions including brain tumors.

中文翻译：

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原发性和转移性乳腺癌免疫治疗的免疫障碍

乳腺癌患者从免疫检查点抑制剂（ICIs）中获得的临床益处有限，这表明存在多种免疫改变，而这些改变无法通过免疫治疗同时恢复正常。越来越多的临床前证据表明，可以利用放射治疗 (RT) 来提高原发性和转移性小鼠乳腺癌对 ICI 的敏感性。然而，针对乳腺癌患者进行的各种将放疗与 ICI 相结合的临床试验显示，其协同作用很少。在这里，我们讨论可能阻止放疗释放 ICI 对乳腺癌患者的治疗潜力的免疫障碍。这些观察结果可能会激发组合疗法的开发，从而使患有包括脑肿瘤在内的多种肿瘤疾病的患者受益。