Obesity-related T cell dysfunction impairs immunosurveillance and increases cancer risk.

Autor: Piening A; Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA., Ebert E; Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA., Gottlieb C; Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA., Khojandi N; Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA., Kuehm LM; Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA., Hoft SG; Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA., Pyles KD; Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO, USA., McCommis KS; Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, MO, USA., DiPaolo RJ; Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA., Ferris ST; Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA., Alspach E; Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA., Teague RM; Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO, USA. ryan.teague@health.slu.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Apr 02; Vol. 15 (1), pp. 2835. Date of Electronic Publication: 2024 Apr 02.
DOI: 10.1038/s41467-024-47359-5
Abstrakt: Obesity is a well-established risk factor for human cancer, yet the underlying mechanisms remain elusive. Immune dysfunction is commonly associated with obesity but whether compromised immune surveillance contributes to cancer susceptibility in individuals with obesity is unclear. Here we use a mouse model of diet-induced obesity to investigate tumor-infiltrating CD8  +  T cell responses in lean, obese, and previously obese hosts that lost weight through either dietary restriction or treatment with semaglutide. While both strategies reduce body mass, only dietary intervention restores T cell function and improves responses to immunotherapy. In mice exposed to a chemical carcinogen, obesity-related immune dysfunction leads to higher incidence of sarcoma development. However, impaired immunoediting in the obese environment enhances tumor immunogenicity, making the malignancies highly sensitive to immunotherapy. These findings offer insight into the complex interplay between obesity, immunity and cancer, and provide explanation for the obesity paradox observed in clinical immunotherapy settings.
(© 2024. The Author(s).)
Databáze: MEDLINE
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