陆军医科大学Yong-hui Lu等研究人员合作发现，射频辐射通过诱导肿瘤浸润性CD8⁺ T细胞和NK细胞的主动转化，将肺转移性黑色素瘤的肿瘤免疫微环境重塑为抗肿瘤表型。2024年3月27日，《中国药理学报》杂志在线发表了这项成果。

研究人员测试了非侵入性射频辐射（RFR）暴露对肿瘤进展和肿瘤免疫微环境（TIME）表型的影响，以及在肺转移性黑色素瘤（PMM）模型中阻断PD-1的抗肿瘤潜力。研究人员通过尾静脉注射B16F10细胞建立了小鼠PMM模型。从注射后第3天开始，小鼠暴露于平均比吸收率为9.7 W/kg的射频辐射，每天1小时，持续14天。暴露于RFR后，收取肺组织并提取RNA进行转录组测序；分离PMM浸润免疫细胞进行单细胞RNA-seq分析。

研究人员发现，RFR暴露通过改变肿瘤浸润免疫细胞的比例和转录谱，明显阻碍了PMM的进展，同时重塑了PMM的TIME。RFR暴露增加了肿瘤浸润CD8⁺ T细胞的活化和细胞毒性特征，尤其是早期活化亚群中与T细胞细胞毒性相关的基因上调。CD8⁺ T细胞中的PD-1检查点通路因暴露于RFR而上调。RFR暴露还增强了NK细胞亚群的细胞毒性特征。

RFR暴露增强了肿瘤浸润CD8⁺ T细胞和NK细胞的效应功能，这得到了细胞毒性分子表达增加的证明。RFR诱导的PMM生长抑制是由RFR激活的CD8⁺ T细胞和NK细胞所介导。研究人员认为，非侵入性RFR暴露可诱导TIME的抗肿瘤重塑，从而抑制肿瘤的进展，这为TIME的启动和与癌症免疫疗法的潜在结合提供了一种前景广阔的新策略。

研究人员表示，肿瘤微环境的免疫抑制是导致肿瘤进展和免疫疗法抗药性的关键因素。诱导TIME已成为提高癌症免疫疗法疗效的一种有前途的策略。

附：英文原文

Title: Radiofrequency radiation reshapes tumor immune microenvironment into antitumor phenotype in pulmonary metastatic melanoma by inducing active transformation of tumor-infiltrating CD8+ T and NK cells

Author: Jiao, Jia-zheng, Zhang, Yang, Zhang, Wen-juan, He, Min-di, Meng, Meng, Liu, Tao, Ma, Qin-long, Xu, Ya, Gao, Peng, Chen, Chun-hai, Zhang, Lei, Pi, Hui-feng, Deng, Ping, Wu, Yong-zhong, Zhou, Zhou, Yu, Zheng-ping, Deng, You-cai, Lu, Yong-hui

Issue&Volume: 2024-03-27

Abstract: Immunosuppression by the tumor microenvironment is a pivotal factor contributing to tumor progression and immunotherapy resistance. Priming the tumor immune microenvironment (TIME) has emerged as a promising strategy for improving the efficacy of cancer immunotherapy. In this study we investigated the effects of noninvasive radiofrequency radiation (RFR) exposure on tumor progression and TIME phenotype, as well as the antitumor potential of PD-1 blockage in a model of pulmonary metastatic melanoma (PMM). Mouse model of PMM was established by tail vein injection of B16F10 cells. From day 3 after injection, the mice were exposed to RFR at an average specific absorption rate of 9.7W/kg for 1h per day for 14 days. After RFR exposure, lung tissues were harvested and RNAs were extracted for transcriptome sequencing; PMM-infiltrating immune cells were isolated for single-cell RNA-seq analysis. We showed that RFR exposure significantly impeded PMM progression accompanied by remodeled TIME of PMM via altering the proportion and transcription profile of tumor-infiltrating immune cells. RFR exposure increased the activation and cytotoxicity signatures of tumor-infiltrating CD8+ T cells, particularly in the early activation subset with upregulated genes associated with T cell cytotoxicity. The PD-1 checkpoint pathway was upregulated by RFR exposure in CD8+ T cells. RFR exposure also augmented NK cell subsets with increased cytotoxic characteristics in PMM. RFR exposure enhanced the effector function of tumor-infiltrating CD8+ T cells and NK cells, evidenced by increased expression of cytotoxic molecules. RFR-induced inhibition of PMM growth was mediated by RFR-activated CD8+ T cells and NK cells. We conclude that noninvasive RFR exposure induces antitumor remodeling of the TIME, leading to inhibition of tumor progression, which provides a promising novel strategy for TIME priming and potential combination with cancer immunotherapy.

DOI: 10.1038/s41401-024-01260-5

Source: https://www.nature.com/articles/s41401-024-01260-5