Obesity-related T cell dysfunction impairs immunosurveillance and increases cancer risk
Abstract 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 u...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-04-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-47359-5 |
| _version_ | 1797219760948117504 |
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| author | Alexander Piening Emily Ebert Carter Gottlieb Niloufar Khojandi Lindsey M. Kuehm Stella G. Hoft Kelly D. Pyles Kyle S. McCommis Richard J. DiPaolo Stephen T. Ferris Elise Alspach Ryan M. Teague |
| author_facet | Alexander Piening Emily Ebert Carter Gottlieb Niloufar Khojandi Lindsey M. Kuehm Stella G. Hoft Kelly D. Pyles Kyle S. McCommis Richard J. DiPaolo Stephen T. Ferris Elise Alspach Ryan M. Teague |
| author_sort | Alexander Piening |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-24T12:38:46Z |
| format | Article |
| id | doaj.art-cd1f556956cf44109479901a6087aca1 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-24T12:38:46Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-cd1f556956cf44109479901a6087aca12024-04-07T11:22:52ZengNature PortfolioNature Communications2041-17232024-04-0115111210.1038/s41467-024-47359-5Obesity-related T cell dysfunction impairs immunosurveillance and increases cancer riskAlexander Piening0Emily Ebert1Carter Gottlieb2Niloufar Khojandi3Lindsey M. Kuehm4Stella G. Hoft5Kelly D. Pyles6Kyle S. McCommis7Richard J. DiPaolo8Stephen T. Ferris9Elise Alspach10Ryan M. Teague11Department of Molecular Microbiology and Immunology, Saint Louis University School of MedicineDepartment of Molecular Microbiology and Immunology, Saint Louis University School of MedicineDepartment of Molecular Microbiology and Immunology, Saint Louis University School of MedicineDepartment of Molecular Microbiology and Immunology, Saint Louis University School of MedicineDepartment of Molecular Microbiology and Immunology, Saint Louis University School of MedicineDepartment of Molecular Microbiology and Immunology, Saint Louis University School of MedicineDepartment of Biochemistry and Molecular Biology, Saint Louis University School of MedicineDepartment of Biochemistry and Molecular Biology, Saint Louis University School of MedicineDepartment of Molecular Microbiology and Immunology, Saint Louis University School of MedicineDepartment of Molecular Microbiology and Immunology, Saint Louis University School of MedicineDepartment of Molecular Microbiology and Immunology, Saint Louis University School of MedicineDepartment of Molecular Microbiology and Immunology, Saint Louis University School of MedicineAbstract 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.https://doi.org/10.1038/s41467-024-47359-5 |
| spellingShingle | Alexander Piening Emily Ebert Carter Gottlieb Niloufar Khojandi Lindsey M. Kuehm Stella G. Hoft Kelly D. Pyles Kyle S. McCommis Richard J. DiPaolo Stephen T. Ferris Elise Alspach Ryan M. Teague Obesity-related T cell dysfunction impairs immunosurveillance and increases cancer risk Nature Communications |
| title | Obesity-related T cell dysfunction impairs immunosurveillance and increases cancer risk |
| title_full | Obesity-related T cell dysfunction impairs immunosurveillance and increases cancer risk |
| title_fullStr | Obesity-related T cell dysfunction impairs immunosurveillance and increases cancer risk |
| title_full_unstemmed | Obesity-related T cell dysfunction impairs immunosurveillance and increases cancer risk |
| title_short | Obesity-related T cell dysfunction impairs immunosurveillance and increases cancer risk |
| title_sort | obesity related t cell dysfunction impairs immunosurveillance and increases cancer risk |
| url | https://doi.org/10.1038/s41467-024-47359-5 |
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