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肥胖肿瘤微环境对 CD8 T 细胞浸润和效应功能的抑制作用。

Suppressive effects of the obese tumor microenvironment on CD8 T cell infiltration and effector function.

机构信息

School of Biochemistry and Immunology, Trinity College Dublin, Dublin, Ireland.

Research Pathology Core Facility, Conway Institute, University College Dublin, Dublin, Ireland.

出版信息

J Exp Med. 2022 Mar 7;219(3). doi: 10.1084/jem.20210042. Epub 2022 Feb 1.

DOI:10.1084/jem.20210042
PMID:35103755
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8932531/
Abstract

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.

摘要

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，我们研究了肥胖对患有子宫内膜癌的小鼠模型和患者中 CD8 T 细胞的影响。我们的研究结果表明，肥胖抑制了 CD8 T 细胞浸润，这与趋化因子产生减少有关。肥胖小鼠的肿瘤驻留 CD8 T 细胞也受到功能抑制，这与氨基酸代谢的抑制有关。同样，我们发现高 BMI 与人类子宫内膜癌中的 CD8 浸润呈负相关，并且体重减轻与九名患者中的六名患者的完全病理反应相关。此外，使用抗 PD-1 的免疫疗法导致瘦鼠和肥胖鼠的肿瘤排斥，并部分恢复了 CD8 代谢和抗肿瘤免疫。这些发现强调了肥胖对 CD8 T 细胞抗肿瘤免疫的抑制作用，这种抑制作用可以通过减轻体重和/或免疫疗法部分逆转。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5df1/8932531/e68b16e1e4b8/JEM_20210042_Fig8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5df1/8932531/e68b16e1e4b8/JEM_20210042_Fig8.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5df1/8932531/0f3c7d0dad94/JEM_20210042_FigS1.jpg
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