Immune checkpoint blockade reprograms systemic immune landscape and tumor microenvironment in obesity-associated breast cancer
Year: 2021
Type: article
Abstract: 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. VIDEO ABSTRACT.
Source: Cell Reports
Authors: Ajeeth K. Pingili, Mehdi Chaib, Laura M. Sipe, Emily J. Miller, Bin Teng, Rahul Sharma, Johnathan R. Yarbro, Sarah Asemota, Qusai Al Abdallah, Tahliyah S. Mims, Tony N. Marion, Deidre Daria, Radhika Sekhri, Alina M. Hamilton, Melissa A. Troester, Heejoon Jo, Hyo Young Choi, D. Neil Hayes, Katherine L. Cook, Ramesh Narayanan, Joseph F. Pierre, Liza Makowski
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,200
Funders: U.S. Department of Defense, American Association for Cancer Research, Mary Kay Foundation, V Foundation for Cancer Research, Susan G. Komen, Triple Negative Breast Cancer Foundation, National Institutes of Health, Health Science Center, University of Tennessee, Harvard Transdisciplinary Research in Energetics and Cancer Center, Harvard University, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, DOD Peer Reviewed Cancer Research Program
Awards: G1017297203, G1143208150, G1494167226, G203802012, G2465765937, MODULATING THE BREAST MICROBIOME TO PREVENT ER+ BREAST CANCER, G2995694289, G324247120, G3397092543, G4119534169, G4507155629, Novel Degraders of the Androgen Receptor (AR) and AR Splice Variants (AR-SVs), G5036744279, G5850682332, G6851758163, G7744010015, G9000067588, G9000091874, G9000124924, G9000171508, G9000232619, G9000241338, Transdisciplinary Research in Energetics and Cancer (TREC) Training Grant, UNC Center for Environmental Health and Susceptibility, Role of microbially-derived metabolites in anti-tumor immunity in breast cancer
OpenAlex ID: W3175536848