Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 219, Issue 3, Pages -Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20210042
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Funding
- Irish Research Council [GOIPD/2018/602]
- Science Foundation Ireland Future Research Leaders Programme [3865]
- European Research Council [StG_679173, R01 AI134861]
- National Institutes of Health metabolic core grant [S10 OD020100]
- Cancer Research Institute CLIP award
- Claudia Adams Barr Program
- Pew Charitable Trusts
- National Institutes of Health [DK123095]
- Science Foundation Ireland Precision Oncology Ireland [18/SPP/3522]
- Lavine Family Fund
- UCD Clinical Research Centre
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Obesity suppresses the activity of CD8 T cells in anti-tumor immunity, and this suppression can be partially reversed by weight loss and immunotherapy.
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. 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.
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