Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran.
Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran.
Biochem Pharmacol. 2020 Apr;174:113787. doi: 10.1016/j.bcp.2019.113787. Epub 2019 Dec 27.
Immunotherapy-based cancer treatment has revolutionized the era of cancer patients recuperation and it has brought a strong hope to treatment of some types of cancers. Metformin, a widely used antidiabetic drug, which has intensely been studied for its anticancer effects, is believed to have positive influences on immune responses against tumor cells. Metformin can affect metabolic pathways within cells mainly through activation of AMPK. Metabolic restriction of tumor microenvironment on effector immune cells is one of the important strategies favoring tumor cells to escape from immunogenic cell death. The metabolism of T cells has an axial role in shaping and supporting immune responses and may have an important role in anticancer immunity, suggesting that the functionality and durability of tumor-specific T cells need sufficient energy and nutrients. Energy biogenesis of tumor-specific cytotoxic T cells has become an interesting field of study and it is suggested that activation and maintenance of effector T cell responses in tumor microenvironment may occur by metabolic reprogramming of T cells. AMPK has been noticed as the main intracellular energy sensor and mitochondrial biogenesis key regulator which can control and regulate metabolic reprogramming in immune cells and increase antitumor immunity. Metabolic reprogramming of T cells to overcome metabolic restriction in tumor microenvironment, maiming effector T cell responses against tumor cells, has been noticed by several studies. Here we represent metformin, an AMPK activator, as a new candidate drug for metabolic reprogramming of tumor-specific T cells to increase the efficacy and accountability of cancer immunotherapy.
基于免疫疗法的癌症治疗已经彻底改变了癌症患者康复的时代，为某些类型的癌症治疗带来了强烈的希望。二甲双胍是一种广泛使用的抗糖尿病药物，因其抗癌作用而受到强烈研究，被认为对针对肿瘤细胞的免疫反应有积极影响。二甲双胍可以通过激活 AMPK 主要影响细胞内的代谢途径。肿瘤微环境对效应免疫细胞的代谢限制是促进肿瘤细胞逃避免疫原性细胞死亡的重要策略之一。T 细胞的代谢在塑造和支持免疫反应中起着关键作用，并且在抗癌免疫中可能具有重要作用，这表明肿瘤特异性 T 细胞的功能和持久性需要足够的能量和营养。肿瘤特异性细胞毒性 T 细胞的能量生成已成为一个有趣的研究领域，据推测，肿瘤微环境中效应 T 细胞反应的激活和维持可能通过 T 细胞的代谢重编程发生。AMPK 已被认为是细胞内主要的能量传感器和线粒体生物发生的关键调节因子，它可以控制和调节免疫细胞中的代谢重编程，并增强抗肿瘤免疫。已经有几项研究注意到 T 细胞的代谢重编程以克服肿瘤微环境中的代谢限制，削弱效应 T 细胞对肿瘤细胞的反应。在这里，我们将 AMPK 激活剂二甲双胍作为一种新的候选药物，用于肿瘤特异性 T 细胞的代谢重编程，以提高癌症免疫治疗的疗效和可及性。
