Department of Urology, University Medical Center Utrecht, The Netherlands.
J Urol. 2012 Aug;188(2):607-14. doi: 10.1016/j.juro.2012.03.116. Epub 2012 Jun 15.
Immune based therapy has gained renewed interest in the search for treatment strategies for metastasized renal cell carcinoma. We determined whether radio frequency ablation combined with interleukin-2 would induce a tumor specific immune response and serve as an in situ vaccine against renal cell carcinoma.
Mice with orthotopic renal tumors were treated with radio frequency ablation combined with interleukin-2, radio frequency ablation only, interleukin-2 only or no treatment as the control. Immunohistochemistry was done to determine which cells were present in the tumor after treatment. In vitro tumor specific cytotoxicity assays were performed with CD8+ T and natural killer cells derived from the spleen of treated mice. To study whether treatment could prevent metastasis or affect the growth of established metastases we induced lung metastasis intravenously before or after treatment and subsequently quantified it.
The number of natural killer, CD4+ and CD8+ T cells was significantly increased in the tumor tissue of radio frequency ablation/interleukin-2 treated mice (p <0.0001). Natural killer and CD8+ T cells showed strong antitumor activity in vitro after combination treatment. Lung metastatic formation was significantly prevented in mice that received combination therapy (p <0.0001). Lung metastases were significantly smaller after combination treatment (vs interleukin-2 p = 0.025).
Radio frequency ablation of the primary tumor combined with interleukin-2 induces a systemic antitumor immune response to renal cell carcinoma, which is much stronger than that of interleukin-2 monotherapy. This effect appears to be mediated by natural killer and CD8+ T cells. It may have an important role in the development of new immunotherapy strategies for renal cell carcinoma.
免疫治疗在寻找转移性肾细胞癌的治疗策略方面重新引起了人们的兴趣。我们确定射频消融联合白细胞介素-2是否会引起肿瘤特异性免疫反应，并作为肾细胞癌的原位疫苗。
将患有原位肾肿瘤的小鼠用射频消融联合白细胞介素-2、仅射频消融、仅白细胞介素-2或不治疗作为对照进行治疗。用免疫组织化学方法确定治疗后肿瘤中存在哪些细胞。用来自治疗小鼠脾脏的 CD8+T 和自然杀伤细胞进行体外肿瘤特异性细胞毒性测定。为了研究治疗是否可以预防转移或影响已建立的转移的生长，我们在治疗前后静脉内诱导肺转移，然后对其进行定量。
射频消融/白细胞介素-2治疗的小鼠肿瘤组织中自然杀伤细胞、CD4+和 CD8+T 细胞的数量显著增加（p<0.0001）。联合治疗后，自然杀伤细胞和 CD8+T 细胞在体外表现出强烈的抗肿瘤活性。接受联合治疗的小鼠肺转移形成明显被预防（p<0.0001）。联合治疗后肺转移明显较小（与白细胞介素-2相比，p=0.025）。
原发性肿瘤的射频消融联合白细胞介素-2可诱导针对肾细胞癌的全身性抗肿瘤免疫反应，其强度明显强于白细胞介素-2单药治疗。这种作用似乎是由自然杀伤细胞和 CD8+T 细胞介导的。它可能在开发肾细胞癌的新免疫治疗策略方面发挥重要作用。
