Suppressive effects of the obese tumor microenvironment on CD8 T cell infiltration and effector function.
Suppressive effects of the obese tumor microenvironment on CD8 T cell infiltration and effector function.
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肥胖肿瘤微环境对CD8 T细胞浸润和效应子功能的抑制作用
DOI：
10.1084/jem.20210042
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发表时间：
2022-03-07
期刊：
影响因子：
--
通讯作者：
Lynch L
中科院分区：
文献类型：
--
作者：
Dyck L;Prendeville H;Raverdeau M;Wilk MM;Loftus RM;Douglas A;McCormack J;Moran B;Wilkinson M;Mills EL;Doughty M;Fabre A;Heneghan H;LeRoux C;Hogan A;Chouchani ET;O'Shea D;Brennan D;Lynch L
Dyck等人。描述肥胖对小鼠癌症模型和人类子宫内膜癌CD8T细胞的抑制作用。使用抗PD-1的免疫疗法对肥胖有效，并部分恢复了小鼠CD8 T细胞的功能和代谢。肥胖是癌症的主要可预防原因之一；然而，人们对肥胖对抗肿瘤免疫的影响知之甚少。在这里，我们研究了肥胖对小鼠模型和子宫内膜癌患者CD8T细胞的影响。我们的研究结果显示，肥胖患者CD8T细胞的浸润受到抑制，这与趋化因子的产生减少有关。在肥胖小鼠中，肿瘤驻留的CD8T细胞也受到功能抑制，这与氨基酸代谢受到抑制有关。同样，我们发现，在9名患者中，高BMI与CD8浸润呈负相关，体重减轻与完全病理反应相关。此外，使用抗PD-1的免疫治疗导致了瘦小和肥胖小鼠的肿瘤排斥反应，并部分恢复了CD8代谢和抗肿瘤免疫。这些发现突显了肥胖对CD8T细胞抗肿瘤免疫的抑制作用，这种抑制作用可以通过减肥和/或免疫治疗部分逆转。
Dyck et al. describe suppressive effects of obesity on CD8 T cells in mouse cancer models and human endometrial cancer. Immunotherapy using anti–PD-1 is effective in obesity and partially restores CD8 T cell function and metabolism in mice. Obesity is one of the leading preventable causes of cancer; however, little is known about the effects of obesity on anti-tumor immunity. Here, we investigated the effects of obesity on CD8 T cells in mouse models and patients with endometrial cancer. Our findings revealed that CD8 T cell infiltration is suppressed in obesity, which was associated with a decrease in chemokine production. Tumor-resident CD8 T cells were also functionally suppressed in obese mice, which was associated with a suppression of amino acid metabolism. Similarly, we found that a high BMI negatively correlated with CD8 infiltration in human endometrial cancer and that weight loss was associated with a complete pathological response in six of nine patients. Moreover, immunotherapy using anti–PD-1 led to tumor rejection in lean and obese mice and partially restored CD8 metabolism and anti-tumor immunity. These findings highlight the suppressive effects of obesity on CD8 T cell anti-tumor immunity, which can partially be reversed by weight loss and/or immunotherapy.
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DOI：
10.1084/jem.20160801
发表时间：
2017-04-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Juneja VR;McGuire KA;Manguso RT;LaFleur MW;Collins N;Haining WN;Freeman GJ;Sharpe AH
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Sharpe AH
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3.3
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Silvestris F
影响因子：
64.5
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Ho PC;Bihuniak JD;Macintyre AN;Staron M;Liu X;Amezquita R;Tsui YC;Cui G;Micevic G;Perales JC;Kleinstein SH;Abel ED;Insogna KL;Feske S;Locasale JW;Bosenberg MW;Rathmell JC;Kaech SM
通讯作者：
Kaech SM
DOI：
10.1073/pnas.1620433114
发表时间：
2017-01-31
影响因子：
11.1
作者：
Chamoto, Kenji;Chowdhury, Partha S.;Honjo, Tasuku
通讯作者：
Honjo, Tasuku
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