研究动态
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放疗对肿瘤微环境的双重影响及其对胃肠道癌和胸部癌免疫治疗耐药性发展的贡献。

Dual effects of radiotherapy on tumor microenvironment and its contribution towards the development of resistance to immunotherapy in gastrointestinal and thoracic cancers.

发表日期:2023
作者: Deyao Zhao, Yingyi Mo, Margarita E Neganova, Yulia Aleksandrova, Edmund Tse, Vladimir N Chubarev, Ruitai Fan, Olga A Sukocheva, Junqi Liu
来源: Frontiers in Cell and Developmental Biology

摘要:

消除肿瘤的成功临床方法包括手术切除、放疗和化疗的组合。放射治疗是癌症治疗方案的关键组成部分之一,可以延长患者的预期寿命。当前的尖端放射治疗研究重点是确定增加癌细胞对放射线的敏感性并激活抗癌免疫机制的方法。放射治疗激活肿瘤微环境(TME)的各种细胞,影响肿瘤生长、血管生成和抗癌免疫。放射治疗被证明可以调节各种 TME 免疫和脉管系统细胞成分的信号传导和抗癌功能,包括肿瘤相关巨噬细胞、树突状细胞、内皮细胞、癌症相关成纤维细胞 (CAF)、自然杀伤细胞和其他 T 细胞亚群。已经检测到辐射的双重效应,包括促进转移效应和氧化应激激活,这表明放疗会触发异质靶点。在这篇综述中,我们批判性地讨论了放疗期间 TME 的激活和血管生成,用于增强新型免疫疗法的效果。重点介绍了信号传导的细胞内、遗传和表观遗传机制以及放疗对免疫反应和氧化应激的临床操作。目前的研究结果表明,放射治疗应被视为免疫治疗的辅助工具,以限制 TME 的促癌作用。为了提高无癌生存率,建议将个性化放射治疗方法与 TME 靶向药物(包括免疫检查点抑制剂)相结合。版权所有 © 2023 Zhu,Mo,Neganova,Aleksandrova,Tse,Chubarev,Fan,Sukocheva 和 Liu。
Successful clinical methods for tumor elimination include a combination of surgical resection, radiotherapy, and chemotherapy. Radiotherapy is one of the crucial components of the cancer treatment regimens which allow to extend patient life expectancy. Current cutting-edge radiotherapy research is focused on the identification of methods that should increase cancer cell sensitivity to radiation and activate anti-cancer immunity mechanisms. Radiation treatment activates various cells of the tumor microenvironment (TME) and impacts tumor growth, angiogenesis, and anti-cancer immunity. Radiotherapy was shown to regulate signaling and anti-cancer functions of various TME immune and vasculature cell components, including tumor-associated macrophages, dendritic cells, endothelial cells, cancer-associated fibroblasts (CAFs), natural killers, and other T cell subsets. Dual effects of radiation, including metastasis-promoting effects and activation of oxidative stress, have been detected, suggesting that radiotherapy triggers heterogeneous targets. In this review, we critically discuss the activation of TME and angiogenesis during radiotherapy which is used to strengthen the effects of novel immunotherapy. Intracellular, genetic, and epigenetic mechanisms of signaling and clinical manipulations of immune responses and oxidative stress by radiotherapy are accented. Current findings indicate that radiotherapy should be considered as a supporting instrument for immunotherapy to limit the cancer-promoting effects of TME. To increase cancer-free survival rates, it is recommended to combine personalized radiation therapy methods with TME-targeting drugs, including immune checkpoint inhibitors.Copyright © 2023 Zhao, Mo, Neganova, Aleksandrova, Tse, Chubarev, Fan, Sukocheva and Liu.