期刊
CELL REPORTS
卷 35, 期 12, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2021.109285
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资金
- UTHSC Center for Cancer Research
- Mary Kay Foundation
- Obesity Society/Susan G. Komen Cancer Challenge award
- Transdisciplinary Research on Energetics and Cancer (TREC) [R25CA203650]
- 2020 American Association for Cancer Research (AACR) Triple Negative Breast Cancer Foundation Research Fellowship
- NIH NCI [U24CA210988, R37CA226969, R01CA253329, UG1CA233333, R01CA229164]
- NIH NIDDK [R01DK127209]
- Tennessee Clinical and Translational Science Institute
- V Foundation
- University of North Carolina University Cancer Research Fund [F31CA257388]
- DOD BCRP [W81XWH-20-1-0014]
- NIH [U01ES019472]
Obesity may enhance the efficacy of immune checkpoint therapies in breast cancer, leading to differential responses to anti-PD-1 treatment in lean and obese mice.
Immune checkpoint blockade (ICB) has improved outcomes in some cancers. A major limitation of ICB is that most patients fail to respond, which is partly attributable to immunosuppression. Obesity appears to improve immune checkpoint therapies in some cancers, but impacts on breast cancer (BC) remain unknown. In lean and obese mice, tumor progression and immune reprogramming were quantified in BC tumors treated with anti-programmed death-1 (PD-1) or control. Obesity augments tumor incidence and progression. Anti-PD-1 induces regression in lean mice and potently abrogates progression in obese mice. BC primes systemic immunity to be highly responsive to obesity, leading to greater immunosuppression, which may explain greater anti-PD-1 efficacy. Anti-PD-1 significantly reinvigorates antitumor immunity despite persistent obesity. Laminin subunit beta-2 (Lamb2), downregulated by anti-PD-1, significantly predicts patient survival. Lastly, a microbial signature associated with anti-PD-1 efficacy is identified. Thus, anti-PD-1 is highly efficacious in obese mice by reinvigorating durable antitumor immunity.
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