Tumor microenvironment induced switch to mitochondrial metabolism promotes suppressive functions in immune cells.

3区 生物学 Q1 Biochemistry, Genetics and Molecular Biology
Sanjay Pandey, Vandana Anang, Michelle M Schumacher
{"title":"Tumor microenvironment induced switch to mitochondrial metabolism promotes suppressive functions in immune cells.","authors":"Sanjay Pandey, Vandana Anang, Michelle M Schumacher","doi":"10.1016/bs.ircmb.2024.07.003","DOIUrl":null,"url":null,"abstract":"<p><p>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).</p>","PeriodicalId":14422,"journal":{"name":"International review of cell and molecular biology","volume":"389 ","pages":"67-103"},"PeriodicalIF":0.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International review of cell and molecular biology","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/bs.ircmb.2024.07.003","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/22 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 0

Abstract

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).

肿瘤微环境诱导的线粒体代谢转换促进了免疫细胞的抑制功能。
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理解癌症的病理和预后至关重要。肿瘤微环境(TME)中的不利条件和细胞压力会对免疫细胞的细胞功能产生深远影响,从而影响肿瘤的进展和免疫反应。葡萄糖水平有限导致的 AMP:ATP 比率升高会激活 AMP 激活蛋白激酶(AMPK),同时抑制雷帕霉素机制靶标(mTOR)和缺氧诱导因子 1-α(HIF-1α)的活性。AMPK、mTOR 和 HIF-1α 活性之间错综复杂的平衡决定了 TME 中免疫细胞的代谢表型。这些代谢表型的变化与免疫细胞的功能密切相关,并在创造有利于肿瘤进展的环境方面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的新陈代谢发生转变,其特点是糖酵解率下降,氧化磷酸化(OXPHOS)和脂肪酸氧化(FAO)率上升。在大多数情况下,新陈代谢的这种转变会影响免疫细胞的效应功能。这种代谢适应会促使免疫细胞降低其效应功能,进入静止或免疫抑制状态,从而支持肿瘤生长。本文以线粒体代谢(OXPHOS 和 FAO)为重点,讨论肿瘤微环境如何改变免疫细胞的代谢,从而导致免疫细胞耐受和肿瘤进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
International review of cell and molecular biology
International review of cell and molecular biology BIOCHEMISTRY & MOLECULAR BIOLOGY-CELL BIOLOGY
CiteScore
7.70
自引率
0.00%
发文量
67
审稿时长
>12 weeks
期刊介绍: International Review of Cell and Molecular Biology presents current advances and comprehensive reviews in cell biology-both plant and animal. Articles address structure and control of gene expression, nucleocytoplasmic interactions, control of cell development and differentiation, and cell transformation and growth. Authored by some of the foremost scientists in the field, each volume provides up-to-date information and directions for future research.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信