了解免疫细胞代谢表型的复杂性及其在肿瘤微环境中的可塑性对于了解癌症的病理学和预后至关重要。肿瘤微环境（TME）中的不利条件和细胞应激对免疫细胞的细胞功能产生深远影响，从而影响肿瘤进展和免疫反应。葡萄糖水平有限导致 AMP:ATP 比率升高，激活 AMP 激活蛋白激酶 (AMPK)，同时抑制雷帕霉素机械靶标 (mTOR) 和缺氧诱导因子 1-α (HIF-1α) 的活性。 AMPK、mTOR 和 HIF-1α 活性之间的复杂平衡决定了 TME 中免疫细胞的代谢表型。代谢表型的这些变化与免疫细胞功能密切相关，并在创造有利于肿瘤进展的环境中发挥着至关重要的作用。营养和氧气供应不足会导致免疫细胞代谢发生变化，其特征是糖酵解减少、氧化磷酸化 (OXPHOS) 和脂肪酸氧化 (FAO) 速率增加。在大多数情况下，新陈代谢的这种转变伴随着这些免疫细胞的效应功能的损害。这种代谢适应促使免疫细胞降低其效应器功能，进入可能支持肿瘤生长的静止或免疫抑制状态。本文讨论了肿瘤微环境如何改变免疫细胞的代谢，从而导致其耐受性和肿瘤进展，重点是线粒体代谢（OXPHOS 和 FAO）。版权所有 © 2024。由 Elsevier Inc. 出版。

Understanding the intricacies of the metabolic phenotype in immune cells and its plasticity within the tumor microenvironment is pivotal in understanding the pathology and prognosis of cancer. Unfavorable conditions and cellular stress in the tumor microenvironment (TME) exert a profound impact on cellular functions in immune cells, thereby influencing both tumor progression and immune responses. Elevated AMP:ATP ratio, a consequence of limited glucose levels, activate AMP-activated protein kinase (AMPK) while concurrently repressing the activity of mechanistic target of rapamycin (mTOR) and hypoxia-inducible factor 1-alpha (HIF-1α). The intricate balance between AMPK, mTOR, and HIF-1α activities defines the metabolic phenotype of immune cells in the TME. These Changes in metabolic phenotype are strongly associated with immune cell functions and play a crucial role in creating a milieu conducive to tumor progression. Insufficiency of nutrient and oxygen supply leads to a metabolic shift in immune cells characterized by a decrease in glycolysis and an increase in oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO) rates. In most cases, this shift in metabolism is accompanied by a compromise in the effector functions of these immune cells. This metabolic adaptation prompts immune cells to turn down their effector functions, entering a quiescent or immunosuppressive state that may support tumor growth. This article discusses how tumor microenvironment alters the metabolism in immune cells leading to their tolerance and tumor progression, with emphasis on mitochondrial metabolism (OXPHOS and FAO).Copyright © 2024. Published by Elsevier Inc.