期刊
NATURE MEDICINE
卷 25, 期 1, 页码 141-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41591-018-0221-5
关键词
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资金
- NIH [R01 CA095572, R01 CA195904, R01 CA214048, P01 CA065493, R01 HL085794]
- California National Primate Research Center [OD011107]
- UC Davis Comprehensive Cancer Center Support Grant (CCSG) [P30 CA093373]
- UC Davis Mouse Metabolic Phenotyping Center (MMPC) [DK092993]
- Intramural Research Program of the NIH
- Intramural Research Program of the NHLBI
- Center for Cancer Research
- Intramural Research Program of the NCI
- NATIONAL CANCER INSTITUTE [R01CA214048, P30CA093373, P01CA065493, P30CA225520, R01CA195904, T32CA009138, R01CA095572] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R24HL085794] Funding Source: NIH RePORTER
- OFFICE OF THE DIRECTOR, NATIONAL INSTITUTES OF HEALTH [P51OD011107] Funding Source: NIH RePORTER
The recent successes of immunotherapy have shifted the paradigm in cancer treatment, but because only a percentage of patients are responsive to immunotherapy, it is imperative to identify factors impacting outcome. Obesity is reaching pandemic proportions and is a major risk factor for certain malignancies, but the impact of obesity on immune responses, in general and in cancer immunotherapy, is poorly understood. Here, we demonstrate, across multiple species and tumor models, that obesity results in increased immune aging, tumor progression and PD-1-mediated T cell dysfunction which is driven, at least in part, by leptin. However, obesity is also associated with increased efficacy of PD-1/PD-L1 blockade in both tumor-bearing mice and clinical cancer patients. These findings advance our understanding of obesity-induced immune dysfunction and its consequences in cancer and highlight obesity as a biomarker for some cancer immunotherapies. These data indicate a paradoxical impact of obesity on cancer. There is heightened immune dysfunction and tumor progression but also greater anti-tumor efficacy and survival after checkpoint blockade which directly targets some of the pathways activated in obesity.
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