Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, United States.
Department of Surgery, Hollings Cancer Center, Medical University of South Carolina, Charleston, SC, United States.
Adv Cancer Res. 2024;162:99-124. doi: 10.1016/bs.acr.2024.05.003. Epub 2024 Jun 13.
It has been well established that in addition to oxygen's vital in cellular respiration, a disruption of oxygen balance can lead to increased stress and oxidative injury. Similarly, reduced oxygen during tumor proliferation and invasion generates a hypoxic tumor microenvironment, resulting in dysfunction of immune cells and providing a conducive milieu for tumors to adapt and grow. Strategies to improve the persistence tumor reactive T cells in the highly oxidative tumor environment are being pursued for enhancing immunotherapy outcomes. To this end, we have focused on various strategies that can help increase or maintain the antioxidant capacity of T cells, thus reducing their susceptibility to oxidative stress/damage. Herein we lay out an overview on the role of oxygen in T cell signaling and how pathways regulating oxidative stress or antioxidant signaling can be targeted to enhance immunotherapeutic approaches for cancer treatment.
已经证实，除了氧气在细胞呼吸中的重要作用外，氧气平衡的破坏会导致应激和氧化损伤增加。同样，肿瘤增殖和侵袭过程中氧气的减少会产生缺氧的肿瘤微环境，导致免疫细胞功能障碍，并为肿瘤的适应和生长提供有利环境。目前正在寻求各种策略来提高在高度氧化的肿瘤环境中持续存在的肿瘤反应性 T 细胞，以增强免疫治疗效果。为此，我们专注于各种策略，以帮助增加或维持 T 细胞的抗氧化能力，从而降低其对氧化应激/损伤的敏感性。本文概述了氧气在 T 细胞信号转导中的作用，以及如何针对调节氧化应激或抗氧化信号的途径来增强癌症治疗的免疫治疗方法。
