Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX 77030, USA; Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA.
Department of Neurological Surgery, Emory University School of Medicine, Atlanta, GA 30322, USA; Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA 30322, USA.
Cell Rep Med. 2023 Jun 20;4(6):101054. doi: 10.1016/j.xcrm.2023.101054. Epub 2023 May 19.
Radiation is commonly used in the treatment of many cancers. However, its effects on anti-tumor immune responses are incompletely understood. Here, we present a detailed immunological analysis of two tumors from a patient with multiple non-small cell lung cancer metastases to the brain. One tumor was resected without treatment; the second was irradiated to a total dose of 30 Gy and resected following further progression. Comprehensive single-cell analysis reveals a substantially reduced immune cell fraction in the irradiated tumor, including the depletion of tissue-resident macrophages and infiltration of pro-inflammatory monocytes. Despite the presence of similar somatic mutations in both tumors, radiation is associated with the depletion of exhausted, tumor-resident T cell clones and their replacement by circulating clones unlikely to contribute to tumor-specific immunity. These results provide insight into the local effects of radiation on anti-tumor immunity and raise important considerations for the combination of radiation and immunotherapy.
辐射常用于治疗多种癌症。然而，其对抗肿瘤免疫反应的影响尚不完全清楚。在这里，我们对一名患有多发性非小细胞肺癌脑转移的患者的两个肿瘤进行了详细的免疫学分析。一个肿瘤未经治疗即被切除；第二个肿瘤接受了 30Gy 的总剂量照射，并在进一步进展后被切除。全面的单细胞分析显示，辐照肿瘤中的免疫细胞比例显著降低，包括组织驻留巨噬细胞耗竭和促炎单核细胞浸润。尽管两个肿瘤存在相似的体细胞突变，但辐射与耗竭性、肿瘤驻留 T 细胞克隆的耗竭有关，并且其被不太可能有助于肿瘤特异性免疫的循环克隆所取代。这些结果深入了解了辐射对抗肿瘤免疫的局部影响，并为辐射与免疫治疗的联合应用提出了重要的考虑因素。
