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Seon Ah Lim
Department of Life Science, Ewha Womans University, Seoul 03760; Research Center for Cellular Homeostasis, Ewha Womans University, Seoul 03760, Korea.
BMB Rep. 2024 Sep;57(9):388-399. doi: 10.5483/BMBRep.2024-0031.
Immunotherapy represents a promising treatment strategy for targeting various tumor types. However, the overall response rate is low due to the tumor microenvironment (TME). In the TME, numerous distinct factors actively induce immunosuppression, restricting the efficacy of anticancer immune reactions. Recently, metabolic reprogramming of tumors has been recognized for its role in modulating the tumor microenvironment to enhance immune cell responses in the TME. Furthermore, recent elucidations underscore the critical role of metabolic limitations imposed by the tumor microenvironment on the effectiveness of antitumor immune cells, guiding the development of novel immunotherapeutic approaches. Hence, achieving a comprehensive understanding of the metabolic requirements of both cancer and immune cells within the TME is pivotal. This insight not only aids in acknowledging the current limitations of clinical practices but also significantly shapes the trajectory of future research endeavors in the domain of cancer immunotherapy. In addition, therapeutic interventions targeting metabolic limitations have exhibited promising potential as combinatory treatments across diverse cancer types. In this review, we first discuss the metabolic barriers in the TME. Second, we explore how the immune response is regulated by metabolites. Finally, we will review the current strategy for targeting metabolism to not simply inhibit tumor growth but also enhance antitumor immune responses. Thus, we could suggest potent combination therapy for improving immunotherapy with metabolic inhibitors. [BMB Reports 2024; 57(9): 388-399].
免疫疗法代表了一种针对多种肿瘤类型的有前途的治疗策略。然而，由于肿瘤微环境（TME）的存在，整体反应率较低。在 TME 中，许多不同的因素积极诱导免疫抑制，限制了抗癌免疫反应的疗效。最近，肿瘤的代谢重编程因其在调节肿瘤微环境以增强 TME 中免疫细胞反应方面的作用而受到关注。此外，最近的研究强调了肿瘤微环境对抗肿瘤免疫细胞有效性施加的代谢限制的关键作用，指导了新型免疫治疗方法的发展。因此，全面了解 TME 中癌症和免疫细胞的代谢需求至关重要。这种认识不仅有助于认识到临床实践的当前局限性，而且还显著塑造了癌症免疫治疗领域未来研究努力的轨迹。此外，针对代谢限制的治疗干预作为多种癌症类型的联合治疗已显示出有希望的潜力。在这篇综述中，我们首先讨论了 TME 中的代谢障碍。其次，我们探讨了代谢物如何调节免疫反应。最后，我们将回顾靶向代谢的当前策略，不仅可以抑制肿瘤生长，还可以增强抗肿瘤免疫反应。因此，我们可以建议使用代谢抑制剂进行有效的联合治疗以改善免疫疗法。[BMB 报告 2024；57(9):388-399]。
