Kheshtchin Nasim, Hadjati Jamshid
Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
Allergy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
J Cell Physiol. 2022 Feb;237(2):1285-1298. doi: 10.1002/jcp.30643. Epub 2021 Nov 19.
The development of new strategies of anticancer immunotherapies has provided promising approaches in the treatment of solid tumors. However, despite the improved survival in responders, most of the patients show incomplete responses with a lack of remarkable clinical improvement. Hypoxia has been identified as a common characteristic of solid tumors contributing to different aspects of tumor progression, including invasion, metastasis, and the creation of the immunosuppressive tumor microenvironment. Hypoxia, through its main mediator, hypoxia-inducible factor-1 (HIF-1) is also associated with the limited efficacy of immunotherapies. Therefore, designing new strategies for immunotherapy implicating therapeutic targeting of HIF-1 molecules may enhance the clinical effectiveness of immunotherapy. Here, we discuss the contribution of hypoxia to the development of the immunosuppressive tumor microenvironment. We will also outline different strategies for targeting hypoxia to provide insight into the therapeutic potential of the application of such strategies to improve the clinical benefit of cancer immunotherapy.
新型抗癌免疫疗法策略的发展为实体瘤治疗提供了有前景的方法。然而，尽管应答者的生存期有所改善，但大多数患者的反应并不完全，缺乏显著的临床改善。缺氧已被确定为实体瘤的一个共同特征，它在肿瘤进展的不同方面发挥作用，包括侵袭、转移以及免疫抑制性肿瘤微环境的形成。缺氧通过其主要介质缺氧诱导因子-1（HIF-1），还与免疫疗法疗效有限有关。因此，设计涉及HIF-1分子治疗靶向的免疫治疗新策略可能会提高免疫治疗的临床效果。在此，我们讨论缺氧对免疫抑制性肿瘤微环境发展的作用。我们还将概述针对缺氧的不同策略，以深入了解应用这些策略改善癌症免疫治疗临床益处的治疗潜力。
