Department of Oncology, James Buchanan Brady Urological Institute, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Int J Radiat Oncol Biol Phys. 2013 Nov 15;87(4):769-76. doi: 10.1016/j.ijrobp.2013.07.015. Epub 2013 Sep 21.
To optimize the combination of ionizing radiation and cellular immunotherapy using a preclinical autochthonous model of prostate cancer.
Transgenic mice expressing a model antigen under a prostate-specific promoter were treated using a platform that integrates cone-beam CT imaging with 3-dimensional conformal therapy. Using this technology we investigated the immunologic and therapeutic effects of combining ionizing radiation with granulocyte/macrophage colony-stimulating factor-secreting cellular immunotherapy for prostate cancer in mice bearing autochthonous prostate tumors.
The combination of ionizing radiation and immunotherapy resulted in a significant decrease in pathologic tumor grade and gross tumor bulk that was not evident with either single-modality therapy. Furthermore, combinatorial therapy resulted in improved overall survival in a preventive metastasis model and in the setting of established micrometastases. Mechanistically, combined therapy resulted in an increase of the ratio of effector-to-regulatory T cells for both CD4 and CD8 tumor-infiltrating lymphocytes.
Our preclinical model establishes a potential role for the use of combined radiation-immunotherapy in locally advanced prostate cancer, which warrants further exploration in a clinical setting.
利用前列腺癌的临床前自发模型，优化电离辐射与细胞免疫疗法的联合应用。
在表达模型抗原的转基因小鼠中，使用一种整合锥形束 CT 成像与三维适形治疗的平台进行治疗。利用这项技术，我们研究了电离辐射与粒细胞/巨噬细胞集落刺激因子分泌细胞免疫疗法联合治疗携带自发前列腺肿瘤的小鼠前列腺癌的免疫和治疗效果。
与单一模式治疗相比，电离辐射和免疫疗法的联合应用导致病理肿瘤分级和大体肿瘤体积显著降低，而单纯单一模式治疗则没有明显效果。此外，联合治疗在预防转移模型和已建立的微转移模型中提高了总生存率。从机制上讲，联合治疗导致 CD4 和 CD8 肿瘤浸润淋巴细胞的效应 T 细胞与调节性 T 细胞的比例增加。
我们的临床前模型为局部晚期前列腺癌中联合使用放化疗提供了潜在的作用，值得在临床环境中进一步探索。
