The Effect of Hypoxia and Hypoxia-Associated Pathways in the Regulation of Antitumor Response: Friends or Foes?
The Effect of Hypoxia and Hypoxia-Associated Pathways in the Regulation of Antitumor Response: Friends or Foes?
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DOI：
10.3389/fimmu.2022.828875
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发表时间：
2022
影响因子：
7.3
通讯作者：
Chouaib S
中科院分区：
文献类型：
--
作者：
Abou Khouzam R;Zaarour RF;Brodaczewska K;Azakir B;Venkatesh GH;Thiery J;Terry S;Chouaib S
缺氧是一种由低氧可用性引起的环境应激源。它通过驱动肿瘤可塑性、异质性、干性和基因组不稳定性来促进实体瘤的进展。缺氧代谢重新编程肿瘤微环境（TME），增加了对酸性，营养缺乏和血管化不良的条件的伤害，这些条件会抑制免疫细胞功能。通过其对关键癌症标志的影响，并通过创造有利于肿瘤存活的物理屏障，缺氧调节肿瘤细胞从安装的免疫反应中逃逸。在低氧TME的背景下，肿瘤细胞-免疫细胞串扰使平衡向对免疫检查点抑制剂（ICI）具有抗性的冷的和免疫抑制的微环境倾斜。尽管如此，有证据表明，缺氧可能是改善ICI反应的一种资产。解决肿瘤免疫结构已经采用了计算机模拟的数字化方法，越来越多的研究应用生物信息学来解卷积TME的细胞和非细胞成分。这些方法还与基于特征的缺氧代理相结合，以进一步剖析动荡的缺氧-免疫关系。在这篇综述中，我们将重点介绍缺氧影响免疫细胞功能的机制，以及在机器学习和计算生物学时代，这种机制如何转化为预测免疫治疗的反应。
Hypoxia is an environmental stressor that is instigated by low oxygen availability. It fuels the progression of solid tumors by driving tumor plasticity, heterogeneity, stemness and genomic instability. Hypoxia metabolically reprograms the tumor microenvironment (TME), adding insult to injury to the acidic, nutrient deprived and poorly vascularized conditions that act to dampen immune cell function. Through its impact on key cancer hallmarks and by creating a physical barrier conducive to tumor survival, hypoxia modulates tumor cell escape from the mounted immune response. The tumor cell-immune cell crosstalk in the context of a hypoxic TME tips the balance towards a cold and immunosuppressed microenvironment that is resistant to immune checkpoint inhibitors (ICI). Nonetheless, evidence is emerging that could make hypoxia an asset for improving response to ICI. Tackling the tumor immune contexture has taken on an in silico, digitalized approach with an increasing number of studies applying bioinformatics to deconvolute the cellular and non-cellular elements of the TME. Such approaches have additionally been combined with signature-based proxies of hypoxia to further dissect the turbulent hypoxia-immune relationship. In this review we will be highlighting the mechanisms by which hypoxia impacts immune cell functions and how that could translate to predicting response to immunotherapy in an era of machine learning and computational biology.
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影响因子：
4.3
作者：
Auletta JJ;Zale EA;Welter JF;Solchaga LA
通讯作者：
Solchaga LA
影响因子：
8.8
作者：
Aras S;Zaidi MR
通讯作者：
Zaidi MR
DOI：
10.1016/j.bbrc.2017.11.183
发表时间：
2018-01-01
影响因子：
3.1
作者：
Bousquet, Paula A.;Sandvik, Joe Alexander;Krengel, Ute
通讯作者：
Krengel, Ute
影响因子：
14.9
作者：
Bader SB;Ma TS;Simpson CJ;Liang J;Maezono SEB;Olcina MM;Buffa FM;Hammond EM
通讯作者：
Hammond EM
影响因子：
29
作者：
Angelin A;Gil-de-Gómez L;Dahiya S;Jiao J;Guo L;Levine MH;Wang Z;Quinn WJ 3rd;Kopinski PK;Wang L;Akimova T;Liu Y;Bhatti TR;Han R;Laskin BL;Baur JA;Blair IA;Wallace DC;Hancock WW;Beier UH
通讯作者：
Beier UH