Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, 60596 Frankfurt/Main, Germany; Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt/Main, Germany.
Institute for Tumor Biology and Experimental Therapy, Georg-Speyer-Haus, 60596 Frankfurt/Main, Germany; Frankfurt Cancer Institute, Goethe University Frankfurt, Frankfurt/Main, Germany; German Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
Redox Biol. 2021 Jun;42:101891. doi: 10.1016/j.redox.2021.101891. Epub 2021 Feb 5.
Reactive oxygen species (ROS) are derivatives of molecular oxygen (O) involved in various physiological and pathological processes. In immune cells, ROS are mediators of pivotal functions such as phagocytosis, antigen presentation and recognition, cytolysis as well as phenotypical differentiation. Furthermore, ROS exert immunosuppressive effects on T and natural killer (NK) cells which is of particular importance in the so-called "tumor microenvironment" (TME) of solid tumors. This term describes the heterogenous group of non-malignant cells including tumor-associated fibroblasts and immune cells, vascular cells, bacteria etc. by which cancer cells are surrounded and with whom they engage in functional crosstalk. Importantly, pharmacological targeting of the TME and, specifically, tumor-associated immune cells utilizing immune checkpoint inhibitors - monoclonal antibodies that mitigate immunosuppression - turned out to be a major breakthrough in the treatment of malignant tumors. In this review, we aim to give an overview of the role that ROS produced in tumor-associated immune cells play during initiation, progression and metastatic outgrowth of solid cancers. Finally, we summarize findings on how ROS in the TME could be targeted therapeutically to increase the efficacy of cancer immunotherapy and discuss factors determining therapeutic success of redox modulation in tumors.
活性氧 (ROS) 是分子氧 (O) 的衍生物，参与各种生理和病理过程。在免疫细胞中，ROS 是吞噬作用、抗原呈递和识别、细胞溶解以及表型分化等关键功能的介质。此外，ROS 对 T 细胞和自然杀伤 (NK) 细胞发挥免疫抑制作用，这在实体瘤的所谓“肿瘤微环境” (TME) 中尤为重要。该术语描述了一组异质的非恶性细胞，包括肿瘤相关成纤维细胞和免疫细胞、血管细胞、细菌等，癌细胞被这些细胞包围，并与它们进行功能串扰。重要的是，针对 TME 的药理学靶向，特别是利用免疫检查点抑制剂（减轻免疫抑制的单克隆抗体）靶向肿瘤相关免疫细胞，已成为治疗恶性肿瘤的重大突破。在这篇综述中，我们旨在概述在实体癌的发生、进展和转移生长过程中，肿瘤相关免疫细胞中产生的 ROS 所起的作用。最后，我们总结了关于如何在 TME 中靶向 ROS 以提高癌症免疫治疗的疗效的研究结果，并讨论了决定肿瘤中氧化还原调节治疗成功的因素。
