Diet-induced obesity accelerates oral carcinogenesis by recruitment and functional enhancement of myeloid-derived suppressor cells.
Diet-induced obesity accelerates oral carcinogenesis by recruitment and functional enhancement of myeloid-derived suppressor cells.
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饮食引起的肥胖通过骨髓源性抑制细胞的募集和功能增强加速口腔癌的发生
DOI：
10.1038/s41419-021-04217-2
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发表时间：
2021-10-14
影响因子：
9
通讯作者：
Xia J
中科院分区：
文献类型：
--
作者：
Peng J;Hu Q;Chen X;Wang C;Zhang J;Ren X;Wang Y;Tao X;Li H;Song M;Cheng B;Wu T;Xia J
虽然肥胖与许多类型癌症的风险和侵袭性增加有关，但它是否促进鳞状细胞癌仍不清楚。为了揭示肥胖在口腔鳞状细胞癌（OSCC）发生和发展中的作用，我们使用4 NQO诱导的OSCC模型小鼠来研究饮食肥胖对癌变的影响。结果显示，高脂饮食（HFD）诱导的肥胖显著促进了OSCC的发生，并改变了局部免疫微环境，导致CD 11b + Gr 1+骨髓源性抑制细胞（MDSCs）扩增。在肥胖症中诱导免疫抑制局部微环境的潜在机制是通过CCL 9/CCR 1轴募集MDSC和通过细胞内脂肪酸摄取增强MDSC免疫抑制功能。此外，临床样本证实了肥胖OSCC患者中浸润的CD 33+（人类MDSC的标志物）细胞的增加，并且来自TCGA数据集的数据证实了CD 33表达与OSCC中的局部脂肪细胞正相关。生存分析显示，脂肪细胞富集和CD 33高表达与口腔鳞癌患者的不良预后相关。引人注目的是，MDSC的耗竭显著改善了4 NQO诱导的模型小鼠中HFD促进的致癌作用。这些发现表明，肥胖也是OSCC的一个重要危险因素，癌症免疫疗法，特别是针对MDSC的癌症免疫疗法，可能在肥胖患者中表现出更大的抗肿瘤疗效。
Although obesity has been associated with an increased risk and aggressiveness of many types of carcinoma, whether it promotes squamous cell carcinoma remains unclear. To reveal the role of obesity in oral squamous cell carcinoma (OSCC) initiation and development, we used 4NQO-induced OSCC model mice to examine the impact of dietary obesity on carcinogenesis. The results showed that high-fat diet (HFD)-induced obesity significantly promoted the incidence of OSCC and altered the local immune microenvironment with the expansion of CD11b+Gr1+myeloid-derived suppressor cells (MDSCs). The underlying mechanism that induced an immunosuppressive local microenvironment in obesity was the recruitment of MDSCs through the CCL9/CCR1 axis and enhancement of MDSC immunosuppressive function via intracellular fatty acid uptake. Furthermore, clinical samples verified the increase in infiltrated CD33+(a marker of human MDSCs) cells in obese OSCC patients, and data from the TCGA dataset confirmed that CD33 expression was positively correlated with local adipocytes in OSCC. Survival analysis showed that enrichment of adipocytes and high expression of CD33 were associated with poor prognosis in OSCC patients. Strikingly, depletion of MDSCs significantly ameliorated HFD-promoted carcinogenesis in 4NQO-induced model mice. These findings indicate that obesity is also an important risk factor for OSCC, and cancer immunotherapy, especially targeting MDSCs, may exhibit greater antitumor efficacy in obese patients.
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NIH-AARP饮食和健康研究中的体型和头颈癌的风险的前瞻性队列研究。
DOI：
10.1158/1055-9965.epi-14-0709-t
发表时间：
2014-11
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Etemadi A;O'Doherty MG;Freedman ND;Hollenbeck AR;Dawsey SM;Abnet CC
通讯作者：
Abnet CC
DOI：
10.1016/s1470-2045(18)30078-0
发表时间：
2018-03
期刊：
The Lancet. Oncology
影响因子：
--
作者：
McQuade JL;Daniel CR;Hess KR;Mak C;Wang DY;Rai RR;Park JJ;Haydu LE;Spencer C;Wongchenko M;Lane S;Lee DY;Kaper M;McKean M;Beckermann KE;Rubinstein SM;Rooney I;Musib L;Budha N;Hsu J;Nowicki TS;Avila A;Haas T;Puligandla M;Lee S;Fang S;Wargo JA;Gershenwald JE;Lee JE;Hwu P;Chapman PB;Sosman JA;Schadendorf D;Grob JJ;Flaherty KT;Walker D;Yan Y;McKenna E;Legos JJ;Carlino MS;Ribas A;Kirkwood JM;Long GV;Johnson DB;Menzies AM;Davies MA
通讯作者：
Davies MA
影响因子：
10.1
作者：
Hossain, Fokhrul;Al-Khami, Amir A.;Ochoa, Augusto C.
通讯作者：
Ochoa, Augusto C.
脂肪细胞来源的 IL-6 和瘦素通过上调 Lysyl Hydroxylase-2 表达促进乳腺癌转移。
影响因子：
8.4
作者：
He, Jin-Yong;Wei, Xiao-Hui;Sun, Li
通讯作者：
Sun, Li
DOI：
10.1136/bmj.j477
发表时间：
2017-02-28
期刊：
BMJ (Clinical research ed.)
影响因子：
--
作者：
Kyrgiou M;Kalliala I;Markozannes G;Gunter MJ;Paraskevaidis E;Gabra H;Martin-Hirsch P;Tsilidis KK
通讯作者：
Tsilidis KK