Parker H. Petit Institute for Bioengineering and Bioscience (J.K., S.N.T.), George W. Woodruff School of Mechanical Engineering (J.K., S.N.T.), and Wallace H. Coulter Department of Biomedical Engineering (S.N.T.), Georgia Institute of Technology, Atlanta, Georgia; Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia (S.N.T.); and Division of Biological Science and Technology, Yonsei University, Wonju, South Korea (J.K.).
Parker H. Petit Institute for Bioengineering and Bioscience (J.K., S.N.T.), George W. Woodruff School of Mechanical Engineering (J.K., S.N.T.), and Wallace H. Coulter Department of Biomedical Engineering (S.N.T.), Georgia Institute of Technology, Atlanta, Georgia; Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia (S.N.T.); and Division of Biological Science and Technology, Yonsei University, Wonju, South Korea (J.K.)
Pharmacol Rev. 2022 Oct;74(4):1146-1175. doi: 10.1124/pharmrev.121.000500.
Despite nearly 30 years of development and recent highlights of nitric oxide (NO) donors and NO delivery systems in anticancer therapy, the limited understanding of exogenous NO's effects on the immune system has prevented their advancement into clinical use. In particular, the effects of exogenously delivered NO differing from that of endogenous NO has obscured how the potential and functions of NO in anticancer therapy may be estimated and exploited despite the accumulating evidence of NO's cancer therapy-potentiating effects on the immune system. After introducing their fundamentals and characteristics, this review discusses the current mechanistic understanding of NO donors and delivery systems in modulating the immunogenicity of cancer cells as well as the differentiation and functions of innate and adaptive immune cells. Lastly, the potential for the complex modulatory effects of NO with the immune system to be leveraged for therapeutic applications is discussed in the context of recent advancements in the implementation of NO delivery systems for anticancer immunotherapy applications. SIGNIFICANCE STATEMENT: Despite a 30-year history and recent highlights of nitric oxide (NO) donors and delivery systems as anticancer therapeutics, their clinical translation has been limited. Increasing evidence of the complex interactions between NO and the immune system has revealed both the potential and hurdles in their clinical translation. This review summarizes the effects of exogenous NO on cancer and immune cells in vitro and elaborates these effects in the context of recent reports exploiting NO delivery systems in vivo in cancer therapy applications.
尽管一氧化氮 (NO) 供体和 NO 输送系统在抗癌治疗方面已经发展了近 30 年，并在最近取得了一些重要进展，但对外源性 NO 对免疫系统的影响的认识有限，阻碍了它们在临床上的应用。特别是，外源性 NO 的作用与内源性 NO 的作用不同，这使得人们难以估计和利用 NO 在抗癌治疗中的潜力和功能，尽管越来越多的证据表明 NO 对免疫系统具有增强癌症治疗的作用。在介绍了它们的基本原理和特性之后，本综述讨论了目前关于 NO 供体和输送系统在调节癌细胞免疫原性以及固有和适应性免疫细胞分化和功能方面的机制理解。最后，根据最近在实施用于癌症免疫治疗应用的 NO 输送系统方面的进展，讨论了 NO 与免疫系统的复杂调节作用在治疗应用中的潜力。
意义陈述：尽管一氧化氮 (NO) 供体和输送系统作为抗癌疗法已经有 30 年的历史，并在最近取得了一些重要进展，但它们的临床转化仍然受到限制。越来越多的证据表明 NO 与免疫系统之间的复杂相互作用，揭示了它们在临床转化中的潜力和障碍。本综述总结了外源性 NO 对体外癌细胞和免疫细胞的影响，并结合最近利用体内 NO 输送系统在癌症治疗应用中的报告阐述了这些影响。
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