Suppressive effects of the obese tumor microenvironment on CD8 T cell infiltration and effector function (vol 219, jem.2021004202072022c, 2022)

被引：0

作者：

Dyck, Lydia

Prendeville, Hannah

Raverdeau, Mathilde

Wilk, Mieszko M.

Loftus, Roisin M.

Douglas, Aaron

McCormack, Janet

Moran, Bruce

Wilkinson, Michael

Mills, Evanna L.

Doughty, Michael

Fabre, Aurelie

Heneghan, Helen

LeRoux, Carel

Hogan, Andrew

Chouchani, Edward T.

O'Shea, Donal

Brennan, Donal

Lynch, Lydia

机构：

[1] School of Biochemistry and Immunology, Trinity College Dublin, Dublin

[2] Research Pathology Core Facility, Conway Institute, University College Dublin, Dublin

[3] Department of Pathology, St. Vincent’s University Hospital, Dublin

[4] University College Dublin Gynaecological Oncology Group, University College Dublin School of Medicine, Mater Misericordiae University Hospital, Dublin

[5] Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA

[6] Department of Cell Biology, Harvard Medical School, Boston, MA

[7] Department of Cellular Pathology, Mater Misericordiae University Hospital, Dublin

[8] School of Medicine, St. Vincent’s University Hospital and University College Dublin, Dublin

[9] Human Health Institute, Department of Biology, Maynooth University, Maynooth

[10] National Children’s Research Centre, Dublin

[11] Systems Biology Ireland, School of Medicine, University College Dublin, Dublin

[12] Brigham and Women’s Hospital, Boston, MA

[13] Harvard Medical School, Boston, MA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2022年 / 219卷 / 03期

关键词：

Innate immunity and inflammation; Metabolism; Tumor immunology;

D O I：

10.1084/jem.2021004202072022c

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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. © 2022 Dyck et al.

引用

页数：1