Tumor Immunotherapy Program, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.
Department of Immunology, The University of Toronto, Toronto, ON, Canada.
Front Immunol. 2021 Aug 12;12:695238. doi: 10.3389/fimmu.2021.695238. eCollection 2021.
Regulation of amino acid availability and metabolism in immune cells is essential for immune system homeostasis and responses to exogenous and endogenous challenges including microbial infection, tumorigenesis and autoimmunity. In myeloid cells the consumption of amino acids such as arginine and tryptophan and availability of their metabolites are key drivers of cellular identity impacting development, functional polarization to an inflammatory or regulatory phenotype, and interaction with other immune cells. In this review, we discuss recent developments and emerging concepts in our understanding of the impact amino acid availability and consumption has on cellular phenotype focusing on two key myeloid cell populations, macrophages and myeloid derived suppressor cells (MDSCs). We also highlight the potential of myeloid-specific of amino acid transporters and catabolic enzymes as immunotherapy targets in a variety of conditions such as cancer and autoimmune disease discussing the opportunities and limitations in targeting these pathways for clinical therapy.
氨基酸可用性和代谢的调节对于免疫系统的稳态和对外源和内源性挑战(包括微生物感染、肿瘤发生和自身免疫)的反应至关重要。在髓样细胞中,氨基酸(如精氨酸和色氨酸)的消耗及其代谢产物的可用性是影响细胞特性的关键驱动因素,影响其发育、向炎症或调节表型的功能极化以及与其他免疫细胞的相互作用。在这篇综述中,我们讨论了我们对氨基酸可用性和消耗对细胞表型影响的理解的最新进展和新出现的概念,重点是两种关键的髓样细胞群体,巨噬细胞和髓源性抑制细胞(MDSCs)。我们还强调了髓样细胞特异性氨基酸转运体和分解代谢酶作为癌症和自身免疫性疾病等多种情况下免疫疗法的潜在靶点,并讨论了针对这些途径进行临床治疗的机会和局限性。