Bloomberg~Kimmel Institute for Cancer Immunotherapy, Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nat Rev Drug Discov. 2019 Sep;18(9):669-688. doi: 10.1038/s41573-019-0032-5. Epub 2019 Jul 30.
Metabolic programming is emerging as a critical mechanism to alter immune cell activation, differentiation and function. Targeting metabolism does not completely suppress or activate the immune system but selectively regulates immune responses. The different metabolic requirements of the diverse cells that constitute an immune response provide a unique opportunity to separate effector functions from regulatory functions. Likewise, cells can be metabolically reprogrammed to promote either their short-term effector functions or long-term memory capacity. Studies in the growing field of immunometabolism support a paradigm of 'cellular selectivity based on demand', in which generic inhibitors of ubiquitous metabolic processes selectively affect cells with the greatest metabolic demand and have few effects on other cells of the body. Targeting metabolism, rather than particular cell types or cytokines, in metabolically demanding processes such as autoimmunity, graft rejection, cancer and uncontrolled inflammation could lead to successful strategies in controlling the pathogenesis of these complex disorders.
代谢编程正在成为改变免疫细胞激活、分化和功能的关键机制。靶向代谢不会完全抑制或激活免疫系统，而是选择性地调节免疫反应。构成免疫反应的不同细胞的不同代谢需求为分离效应功能和调节功能提供了独特的机会。同样，细胞可以被代谢重编程以促进其短期效应功能或长期记忆能力。免疫代谢领域的研究支持“基于需求的细胞选择性”范例，其中普遍存在的代谢过程的通用抑制剂选择性地影响代谢需求最大的细胞，而对身体的其他细胞几乎没有影响。在自身免疫、移植物排斥、癌症和失控炎症等代谢需求高的过程中靶向代谢，而不是特定的细胞类型或细胞因子，可能会导致控制这些复杂疾病发病机制的成功策略。
