Cellular and Molecular Research Center, Cellular and Molecular Medicine Institute, Urmia University of Medical Sciences, Urmia, Iran.
Department of Clinical Biochemistry, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.
Immunol Lett. 2020 Apr;220:32-37. doi: 10.1016/j.imlet.2020.01.006. Epub 2020 Jan 23.
Despite the prominent progress in understanding cancer immunosurveillance mechanisms, there are some types of problems which have been identified to hinder effective and successful immunotherapy of cancers. Such problems have been ascribed to the tumor abilities in the creation of a tolerant milieu that can impair immune responses against cancer cells. In the present study, we represent possible approaches for metabolic reprogramming of T cells in cancer immunotherapy to overcome tumor metabolic impositions on immune responses against cancer cells. Metabolic suppression of effector immune cells in tumor milieu is one of the important strategies recruited by tumor cells to escape from immunogenic cell death. We have investigated the metabolic reprogramming of T cells as a method and a possible new target for cancer immunotherapy. Synergic effects of PPAR ligands in immunotherapy of cancers on the metabolic reprogramming of T cells have been noticed by several studies as a new target of cancer immunotherapy. The current wealth of data like this promises a future scenario which the consideration of metabolic restriction in the tumor microenvironment and administration of therapeutic agents such as PPAR ligands to overcome metabolic restrictions on T cells (refreshing their functionality) may be effective and enhance the accountability and efficacy of cancer immunotherapy.
尽管在理解癌症免疫监视机制方面取得了显著进展,但仍存在一些问题被认为会阻碍癌症的有效和成功免疫治疗。这些问题归因于肿瘤创造耐受环境的能力,这可能会损害针对癌细胞的免疫反应。在本研究中,我们提出了在癌症免疫治疗中对 T 细胞进行代谢重编程的可能方法,以克服肿瘤对针对癌细胞的免疫反应的代谢限制。在肿瘤微环境中抑制效应免疫细胞的代谢是肿瘤细胞逃避免疫原性细胞死亡的重要策略之一。我们已经研究了 T 细胞的代谢重编程作为癌症免疫治疗的一种方法和可能的新靶点。几项研究注意到,PPAR 配体在癌症免疫治疗中的协同作用可促进 T 细胞的代谢重编程,这是癌症免疫治疗的一个新靶点。目前,大量这样的数据表明,在肿瘤微环境中考虑代谢限制以及使用治疗剂(如 PPAR 配体)来克服 T 细胞的代谢限制(使其功能恢复活力)可能是有效的,并增强癌症免疫治疗的效果和功效。