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The therapeutic implications of immunosuppressive tumor aerobic glycolysis
Cellular & Molecular Immunology ( IF 24.1 ) Pub Date : 2021-07-08 , DOI: 10.1038/s41423-021-00727-3
Bradley I Reinfeld 1 , W Kimryn Rathmell 1 , Tae Kon Kim 1 , Jeffrey C Rathmell 2
Affiliation  

In 2011, Hanahan and Weinberg added “Deregulating Cellular Energetics” and “Avoiding Immune Destruction” to the six previous hallmarks of cancer. Since this seminal paper, there has been a growing consensus that these new hallmarks are not mutually exclusive but rather interdependent. The following review summarizes how founding genetic events for tumorigenesis ultimately increase tumor cell glycolysis, which not only supports the metabolic demands of malignancy but also provides an immunoprotective niche, promoting malignant cell proliferation, maintenance and progression. The mechanisms by which altered metabolism contributes to immune impairment are multifactorial: (1) the metabolic demands of proliferating tumor cells and activated immune cells are similar, thus creating a situation where immune cells may be in competition for key nutrients; (2) the metabolic byproducts of aerobic glycolysis directly inhibit antitumor immunity while promoting a regulatory immune phenotype; and (3) the gene programs associated with the upregulation of glycolysis also result in the generation of immunosuppressive cytokines and metabolites. From this perspective, we shed light on important considerations for the development of new classes of agents targeting cancer metabolism. These types of therapies can impair tumor growth but also pose a significant risk of stifling antitumor immunity.



中文翻译:

免疫抑制性肿瘤有氧糖酵解的治疗意义

2011 年,Hanahan 和 Weinberg 将“细胞能量失调”和“避免免疫破坏”添加到之前的六个癌症特征中。自这篇开创性论文以来,越来越多的人认为这些新标志不是相互排斥的,而是相互依存的。以下综述总结了肿瘤发生的遗传事件如何最终增加肿瘤细胞糖酵解,这不仅支持恶性肿瘤的代谢需求,还提供免疫保护生态位,促进恶性细胞增殖、维持和进展。代谢改变导致免疫损伤的机制是多方面的:(1)增殖的肿瘤细胞和激活的免疫细胞的代谢需求相似,从而造成免疫细胞可能竞争关键营养素的情况;(2) 有氧糖酵解的代谢副产物直接抑制抗肿瘤免疫,同时促进调节免疫表型;(3) 与糖酵解上调相关的基因程序也会导致免疫抑制性细胞因子和代谢物的产生。从这个角度来看,我们阐明了开发针对癌症代谢的新型药物的重要考虑因素。这些类型的疗法会损害肿瘤生长,但也会造成抑制抗肿瘤免疫力的重大风险。我们阐明了开发针对癌症代谢的新型药物的重要考虑因素。这些类型的疗法会损害肿瘤生长,但也会造成抑制抗肿瘤免疫力的重大风险。我们阐明了开发针对癌症代谢的新型药物的重要考虑因素。这些类型的疗法会损害肿瘤生长,但也会造成抑制抗肿瘤免疫力的重大风险。

更新日期:2021-07-08
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