Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment.
Altered acetyl-CoA metabolism presents a new potential immunotherapy target in the obese lung microenvironment.
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DOI：
10.1186/s40170-022-00292-x
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发表时间：
2022-10-26
影响因子：
5.9
通讯作者：
中科院分区：
文献类型：
--
作者：
与“肥胖悖论”相反的是，流行病学证据表明，中心性或内脏肥胖与患肺癌的风险更高有关。“肥胖悖论”源于回顾研究，依靠身体质量指数来定义肥胖。大约60%的肺癌高危人群或已经患有早期疾病的人超重或肥胖。切除的患者肿瘤和小鼠肺肿瘤模型的研究结果表明，肥胖抑制了肿瘤微环境(TME)中的免疫活性，促进了疾病的进展。与此相一致，我们观察到在小鼠肿瘤以及人类和小鼠的呼吸道中，免疫抑制调节性T(Treg)细胞的存在和表型都有显著的肥胖特异性增强。利用直接代谢组学测量和从RNA测序数据中可靠的推断分析，我们首次证明内脏脂肪通过调节失调的乙酰辅酶A代谢改变肺微环境，促进免疫抑制和肺癌发生。网上版载有补充材料，可在10.1186/s4017022-00292-x查阅。
Contrary to the “obesity paradox,” which arises from retrospective studies relying on body mass index to define obesity, epidemiologic evidence suggests central or visceral obesity is associated with a higher risk for the development of lung cancer. About 60% of individuals at high risk for developing lung cancer or those already with early-stage disease are either overweight or obese. Findings from resected patient tumors and mouse lung tumor models show obesity dampens immune activity in the tumor microenvironment (TME) encouraging disease progression. In line with this, we have observed a marked, obesity-specific enhancement in the presence and phenotype of immunosuppressive regulatory T (Treg) cells in murine tumors as well as the airways of both humans and mice. Leveraging direct metabolomic measurements and robust inferred analyses from RNA-sequencing data, we here demonstrate for the first time that visceral adiposity alters the lung microenvironment via dysregulated acetyl-CoA metabolism in a direction that facilitates immune suppression and lung carcinogenesis. The online version contains supplementary material available at 10.1186/s40170-022-00292-x.
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DOI：
10.1007/978-1-4939-6527-4_21
发表时间：
2017
期刊：
Methods in molecular biology (Clifton, N.J.)
影响因子：
--
作者：
Jiao J;Han R;Hancock WW;Beier UH
通讯作者：
Beier UH
影响因子：
4.4
作者：
Hawse, William F.;Cattley, Richard T.;Wendell, Stacy G.
通讯作者：
Wendell, Stacy G.
影响因子：
28.2
作者：
Cantor JR;Sabatini DM
通讯作者：
Sabatini DM
DOI：
10.1007/978-3-319-77736-8_1
发表时间：
2018-01-01
期刊：
HETEROGENEITY OF CANCER METABOLISM
影响因子：
--
作者：
Bose, Sminu;Le, Anne
通讯作者：
Le, Anne
影响因子：
28.2
作者：
Carrer, Alessandro;Trefely, Sophie;Wellen, Kathryn E.
通讯作者：
Wellen, Kathryn E.