Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain.
Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Córdoba, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain; Unidad de Gestión Clínica de Oncología Médica, Hospital Reina Sofía, Universidad de Córdoba, Córdoba, Spain.
Transl Res. 2019 Aug;210:99-108. doi: 10.1016/j.trsl.2019.03.003. Epub 2019 Mar 15.
In recent years, an increasing number of studies have shown that there is an important connection between nitric oxide (NO) and the pathology of malignant diseases, but we are far from a complete comprehension of how this simple diatomic molecule contributes to tumorigenesis. The emerging identification of immune-mediated mechanisms regulated by NO may help to unravel the intricate and complex relationships between NO and cancer. Therefore, this review provides a summary of recent advances in our understanding of the immunomodulatory role of NO in cancer, and in particular the role of this pleiotropic signaling molecule as an immunosuppressive mediator in the tumor microenvironment. We will discuss the participation of NO in the different strategies used by tumors to escape from immune system-mediated recognition, including the acquisition of stem cell like capacities by tumor cells and the metabolic reprogramming of tumor infiltrating immune cells. Finally, we will also discuss different therapeutic strategies directed against NO for abating the immunosuppressive tumor microenvironment and to increase the efficacy of immunotherapy in cancer.
近年来，越来越多的研究表明，一氧化氮（NO）与恶性疾病的病理学之间存在重要联系，但我们远未完全理解这种简单双原子分子如何促进肿瘤发生。新兴的被 NO 调控的免疫介导机制的鉴定，可能有助于揭示 NO 与癌症之间复杂而又相互关联的关系。因此，本综述概述了我们对 NO 在癌症中免疫调节作用的最新认识，特别是作为肿瘤微环境中免疫抑制介质的这种多效信号分子的作用。我们将讨论 NO 参与肿瘤逃避免疫系统介导的识别的不同策略，包括肿瘤细胞获得类似干细胞的能力以及肿瘤浸润免疫细胞的代谢重编程。最后，我们还将讨论针对 NO 的不同治疗策略，以减轻免疫抑制性肿瘤微环境并提高癌症免疫治疗的疗效。
