Minimally Invasive Tumor Therapies Center, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, P.R.China.
Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, P.R.China.
Cell Cycle. 2023 Jan;22(2):242-254. doi: 10.1080/15384101.2022.2112007. Epub 2022 Aug 18.
The study was designed to evaluate the efficiency of microwave ablation (MWA) in combination with anti-programmed death receptor 1 (anti-PD-1)/cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) in renal cell carcinoma (RCC) treatment. After tumors were established on C57/BL6 mice, MWA treatment and/or immune checkpoint inhibitor (ICI) treatment to the mice were performed. Tumor volume was recorded every 7 days. A rechallenge test was conducted on mice with tumors in the left kidney to explore the systemic establishment of antitumor immunity on day 7. In this study, during the 21-day observation period, tumors were continued to grow in all groups. However, compared with the tumor growth rate in MWA or control group, the rate in the ICI or MWA+ICI groups was decreased. Moreover, the population of CD8+T-cells was increased only in the MWA+ICI group, while that of regulatory T cells was decreased in the MWA, ICI, and MWA+ICI groups. Additionally, the MWA+ICI group had the highest interferon-γ level among all groups. Furthermore, histopathological examination revealed that CTLA-4 expression in distant tumors was reduced in the ICI and MWA + ICI groups. MWA treatment increased PD-L1/PD-1 expression; however, after the combination treatment with ICI, PD-L1/PD-1 expression was decreased. According to the rechallenge test, mice (16.7%) in the MWA group, ICI group (50%), and MWA+ICI group (66.7%) exhibited successful tumor rejection, whereas no mice in the control group exhibited the capability of tumor rejection. Overall, the systemic antitumor immunity induced by MWA was boosted when combined with anti-PD-1/CTLA-4 treatment in an RCC murine model.
这项研究旨在评估微波消融（MWA）联合抗程序性死亡受体 1（anti-PD-1）/细胞毒性 T 淋巴细胞相关抗原 4（CTLA-4）在肾细胞癌（RCC）治疗中的疗效。在 C57/BL6 小鼠上建立肿瘤后，对小鼠进行 MWA 治疗和/或免疫检查点抑制剂（ICI）治疗。每 7 天记录一次肿瘤体积。在左肾有肿瘤的小鼠上进行再挑战试验，以在第 7 天探索全身抗肿瘤免疫的建立。在这项研究中，在 21 天的观察期内，所有组的肿瘤都在继续生长。然而，与 MWA 或对照组的肿瘤生长速度相比，ICI 或 MWA+ICI 组的肿瘤生长速度降低。此外，仅在 MWA+ICI 组中 CD8+T 细胞的数量增加，而在 MWA、ICI 和 MWA+ICI 组中调节性 T 细胞的数量减少。此外，MWA+ICI 组的干扰素-γ水平在所有组中最高。此外，组织病理学检查显示，ICI 和 MWA+ICI 组中远处肿瘤的 CTLA-4 表达减少。MWA 治疗增加了 PD-L1/PD-1 的表达；然而，在与 ICI 联合治疗后，PD-L1/PD-1 的表达减少。根据再挑战试验，MWA 组（16.7%）、ICI 组（50%）和 MWA+ICI 组（66.7%）的小鼠成功排斥肿瘤，而对照组的小鼠均未表现出排斥肿瘤的能力。总的来说，在 RCC 小鼠模型中，MWA 联合抗 PD-1/CTLA-4 治疗可增强全身抗肿瘤免疫。
