Department of Radiation Medicine, Roswell Park Cancer Institute, Buffalo, New York.
Department of Urology, Roswell Park Cancer Institute, Buffalo, New York.
Clin Cancer Res. 2017 Sep 1;23(17):5055-5065. doi: 10.1158/1078-0432.CCR-16-2946. Epub 2017 Jun 19.
While stereotactic body radiotherapy (SBRT) can reduce tumor volumes in patients with metastatic renal cell carcinoma (mRCC), little is known regarding the immunomodulatory effects of high-dose radiation in the tumor microenvironment. The main objectives of this pilot study were to assess the safety and feasibility of nephrectomy following SBRT treatment of patients with mRCC and analyze the immunological impact of high-dose radiation. Human RCC cell lines were irradiated and evaluated for immunomodulation. In a single-arm feasibility study, patients with mRCC were treated with 15 Gray SBRT at the primary lesion in a single fraction followed 4 weeks later by cytoreductive nephrectomy. RCC specimens were analyzed for tumor-associated antigen (TAA) expression and T-cell infiltration. The trial has reached accrual (ClinicalTrials.gov identifier: NCT01892930). RCC cells treated with radiation had increased TAA expression compared with untreated tumor cells. Fourteen patients received SBRT followed by surgery, and treatment was well-tolerated. SBRT-treated tumors had increased expression of the immunomodulatory molecule calreticulin and TAA (CA9, 5T4, NY-ESO-1, and MUC-1). Ki67 -proliferating CD8 T cells and FOXP3 cells were increased in SBRT-treated patient specimens in tumors and at the tumor-stromal interface compared with archived patient specimens. It is feasible to perform nephrectomy following SBRT with acceptable toxicity. Following SBRT, patient RCC tumors have increased expression of calreticulin, TAA, as well as a higher percentage of proliferating T cells compared with archived RCC tumors. Collectively, these studies provide evidence of immunomodulation following SBRT in mRCC. .
立体定向体部放疗（SBRT）可使转移性肾细胞癌（mRCC）患者的肿瘤体积缩小，但对肿瘤微环境中高剂量放疗的免疫调节作用知之甚少。本研究的主要目的是评估 SBRT 治疗 mRCC 患者后行肾切除术的安全性和可行性，并分析高剂量放疗的免疫影响。用 SBRT 照射人肾细胞癌细胞系并评估其免疫调节作用。在一项单臂可行性研究中，mRCC 患者在单个部位接受 15 戈瑞 SBRT 单次照射，4 周后行减瘤性肾切除术。分析肾细胞癌标本的肿瘤相关抗原（TAA）表达和 T 细胞浸润。该试验已达到入组（ClinicalTrials.gov 标识符：NCT01892930）。与未处理的肿瘤细胞相比，用辐射处理的肾细胞癌细胞具有更高的 TAA 表达。14 例患者接受 SBRT 后行手术治疗，且治疗耐受性良好。SBRT 治疗的肿瘤具有更高的免疫调节分子钙网蛋白和 TAA（CA9、5T4、NY-ESO-1 和 MUC-1）表达。与存档的患者标本相比，SBRT 治疗的患者标本中肿瘤和肿瘤基质界面的 Ki67 增殖 CD8 T 细胞和 FOXP3 细胞增加。与存档的肾细胞癌肿瘤相比，SBRT 后患者肾细胞癌肿瘤具有更高的钙网蛋白、TAA 表达以及更高比例的增殖 T 细胞。这些研究为 mRCC 中 SBRT 后免疫调节提供了证据。
