The therapeutic implications of immunosuppressive tumor aerobic glycolysis.
The therapeutic implications of immunosuppressive tumor aerobic glycolysis.
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DOI：
10.1038/s41423-021-00727-3
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发表时间：
2022-01
影响因子：
24.1
通讯作者：
Rathmell JC
中科院分区：
文献类型：
--
作者：
Reinfeld BI;Rathmell WK;Kim TK;Rathmell JC
2011年，Hanahan和Weinberg将“解除细胞能量调节”和“避免免疫破坏”添加到癌症之前的六个特征中。自从这篇开创性的论文发表以来，越来越多的人认为，这些新的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，而且提供免疫保护生态位，促进恶性细胞的增殖、维持和进展。代谢改变导致免疫损伤的机制是多因素的：(1)增殖的肿瘤细胞和活化的免疫细胞的代谢需求是相似的，从而造成免疫细胞可能竞争关键营养物质的情况；(2)有氧糖酵解的代谢副产物直接抑制抗肿瘤免疫，同时促进一种调节性免疫表型；(3)与糖酵解上调相关的基因程序也导致免疫抑制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。这些类型的治疗可以损害肿瘤生长，但也有抑制抗肿瘤免疫的重大风险。
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.
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影响因子：
29
作者：
Cascone T;McKenzie JA;Mbofung RM;Punt S;Wang Z;Xu C;Williams LJ;Wang Z;Bristow CA;Carugo A;Peoples MD;Li L;Karpinets T;Huang L;Malu S;Creasy C;Leahey SE;Chen J;Chen Y;Pelicano H;Bernatchez C;Gopal YNV;Heffernan TP;Hu J;Wang J;Amaria RN;Garraway LA;Huang P;Yang P;Wistuba II;Woodman SE;Roszik J;Davis RE;Davies MA;Heymach JV;Hwu P;Peng W
通讯作者：
Peng W
影响因子：
11.2
作者：
Barsoum, Ivraym B.;Smallwood, Chelsea A.;Graham, Charles H.
通讯作者：
Graham, Charles H.
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
影响因子：
8
作者：
Beckermann, Kathryn E.;Hongo, Rachel;Rathmell, Jeffrey C.
通讯作者：
Rathmell, Jeffrey C.
影响因子：
17.1
作者：
Chan DA;Sutphin PD;Nguyen P;Turcotte S;Lai EW;Banh A;Reynolds GE;Chi JT;Wu J;Solow-Cordero DE;Bonnet M;Flanagan JU;Bouley DM;Graves EE;Denny WA;Hay MP;Giaccia AJ
通讯作者：
Giaccia AJ