Diet-induced obesity alters dendritic cell function in the presence and absence of tumor growth.
Diet-induced obesity alters dendritic cell function in the presence and absence of tumor growth.
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饮食诱导的肥胖症在存在和不存在肿瘤生长的情况下改变了树突状细胞的功能。
DOI：
10.4049/jimmunol.1100587
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发表时间：
2012-08-01
期刊：
影响因子：
--
通讯作者：
Norian LA
中科院分区：
文献类型：
--
作者：
James BR;Tomanek-Chalkley A;Askeland EJ;Kucaba T;Griffith TS;Norian LA
在美国，肥胖是一个日益严重的健康问题，并与几种癌症的发病风险增加有关，包括肾细胞癌（RCC）。尽管如此，人们对肥胖对抗肿瘤免疫的影响知之甚少。由于树突状细胞（DC）是抗肿瘤免疫的关键调节因子，我们研究了肥胖和肿瘤生长对DC功能的联合影响。采用饮食性肥胖（DIO）模型，评估了原位RCC小鼠和无肿瘤对照小鼠的DC功能。无肿瘤的DIO小鼠血清细胞因子和趋化因子谱发生了深刻的改变，15种蛋白上调，包括IL-1α、IL-17和LIF。无肿瘤的DIO小鼠刺激初始T细胞扩增能力受损的常规脾DC百分比升高，尽管它们的表型与正常体重（NW）对照相似。在DIO小鼠中，在没有治疗的情况下，肾内RCC肿瘤攻击导致T细胞抑制性DC局部浸润增加，并加速早期肿瘤生长。在给予dc依赖性免疫治疗后，NW小鼠中已建立的RCC肿瘤消退。同样的免疫治疗在DIO小鼠中无效，其特征是在荷瘤肾脏中积累了调节性DC，产生ifn γ的CD8 T细胞的局部浸润减少，肿瘤生长进展。我们的研究结果表明，肥胖作为合并症的存在会损害dc依赖性抗肿瘤免疫疗法的疗效。
Obesity is a mounting health concern in the United States, and is associated with an increased risk for developing several cancers, including renal cell carcinoma (RCC). Despite this, little is known regarding the impact of obesity on antitumor immunity. As dendritic cells (DC) are critical regulators of antitumor immunity, we examined the combined effects of obesity and tumor outgrowth on DC function. Using a diet-induced obesity (DIO) model, DC function was evaluated in mice bearing orthotopic RCC and in tumor-free controls. Tumor-free DIO mice had profoundly altered serum cytokine and chemokine profiles, with upregulation of 15 proteins, including IL-1α, IL-17, and LIF. Tumor-free DIO mice had elevated percentages of conventional splenic DC that were impaired in their ability to stimulate naive T cell expansion, although they were phenotypically similar to normal weight (NW) controls. In DIO mice, intra-renal RCC tumor challenge in the absence of therapy led to increased local infiltration by T cell-suppressive DC and accelerated early tumor outgrowth. Following administration of a DC-dependent immunotherapy, established RCC tumors regressed in NW mice. The same immunotherapy was ineffective in DIO mice, and was characterized by an accumulation of regulatory DC in tumor-bearing kidneys, decreased local infiltration by IFNγ-producing CD8 T cells, and progressive tumor outgrowth. Our results suggest that the presence of obesity as a co-morbidity can impair the efficacy of DC-dependent antitumor immunotherapies.
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肥胖可促进雌性扎克大鼠蒽诱导的乳腺肿瘤发育的7,12-二甲基苯子。
DOI：
10.1186/bcr1263
发表时间：
2005
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Hakkak R;Holley AW;Macleod SL;Simpson PM;Fuchs GJ;Jo CH;Kieber-Emmons T;Korourian S
通讯作者：
Korourian S
影响因子：
5
作者：
Holoch, Peter A.;Griffith, Thomas S.
通讯作者：
Griffith, Thomas S.
影响因子：
4
作者：
Drake, Justin M.;Gabriel, Curtis L.;Henry, Michael D.
通讯作者：
Henry, Michael D.
DOI：
10.4161/cc.8.9.8348
发表时间：
2009-05-01
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Gao W;Thompson L;Zhou Q;Putheti P;Fahmy TM;Strom TB;Metcalfe SM
通讯作者：
Metcalfe SM
影响因子：
2.9
作者：
Cleary, MP;Grande, JP;Maihle, NJ
通讯作者：
Maihle, NJ