Obesity-driven inflammation and immune dysregulation in cancer development and progression
4 affiliations
- 1Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
- 2Department of Exercise and Sport Science, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
- 3Nutrition Research Institute, University of North Carolina at Chapel Hill, Kannapolis, NC, United States
- 4Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States
Abstract
Obesity increases the risk and progression of at least 13 types of cancer. Although the epidemiologic links between excess adiposity and these cancers are well documented, the biological mechanisms linking obesity to carcinogenesis and tumor progression remain incompletely understood. White adipose tissue in obesity is a source of inflammatory and immunosuppressive signals that act systemically, driving metabolic, inflammatory, and immune dysfunction whose consequences differ across tumor types. As adipose tissue expands and adipocytes enlarge, the blood supply becomes inadequate, leading to hypoxia, fibrosis, lipolytic stress, macrophage recruitment, and chronic low-grade inflammation. These obesity-induced perturbations generate endocrine, cytokine, lipid, and metabolic signals that act systemically, within the tumor microenvironment (TME), and/or cell-intrinsically to activate oncogenic and tumor-promoting pathways. The same signals reshape innate and adaptive immunity, promoting tumor-permissive macrophage states and myeloid-derived suppressor cell expansion, while the effector arms weaken as antigen presentation, natural killer cell and T cell function all decline. This review synthesizes current evidence linking obesity-associated inflammation and immune dysregulation to cancer initiation, progression, and treatment responses across multiple obesity-related cancers. Emphasis is placed on adipose tissue inflammation, myeloid cell biology, T cell immunometabolism, endocrine-inflammatory crosstalk, and the relationship between obesity and immunotherapy. Finally, we discuss translational opportunities for preventing or intercepting obesity-related cancers, including weight loss achieved through lifestyle, surgical, or pharmacologic approaches, with an emphasis on GLP-1 receptor agonists given their substantial efficacy, rapid clinical uptake, and potential to reshape obesity-related cancer prevention and survivorship strategies. Defining the metabolic, immune, and inflammatory phenotypes that drive obesity-associated cancer risk and progression will be essential for developing more precise, mechanism-based strategies for prevention, treatment, and survivorship care.
Related
- Benzene exposure in relation to the development of glycemic dysregulation and type 2 diabetes mediated by oxidative stress and aggravated by inflammation in a repeated-measure prospective cohort study of Chinese adults
- Lipid Dysregulation and Impaired Resolution of Inflammation in Genetic Forms of Parkinson’s Disease: Potential Links and Knowledge Gaps
- Convergent Immunopathology in Influenza-Associated Encephalopathy: CD3+ CD4+ T Cell Depletion, IL-6-Mediated Inflammation, and Complement C3 Dysregulation
- Yiguanjian alleviates ocular surface inflammation and lacrimal gland immune dysregulation in experimental dry eye disease: evidence from in vivo and in vitro models
- Heart and Brain: Linking Obesity-Related Inflammation, Cardiovascular Disease and Cognitive Function
BibTeX
@article{pandey2026obesitydriven,
title = {{Obesity-driven inflammation and immune dysregulation in cancer development and progression}},
author = {Pritika Pandey and Jeb F. Struder and Erika T. Rezeli and Evan M. Paules and Stephen D. Hursting and Michael F. Coleman and Kristin A. Altwegg},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1947958},
url = {https://doi.org/10.3389/fonc.2026.1947958},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Obesity-driven inflammation and immune dysregulation in cancer development and progression
AU - Pritika Pandey
AU - Jeb F. Struder
AU - Erika T. Rezeli
AU - Evan M. Paules
AU - Stephen D. Hursting
AU - Michael F. Coleman
AU - Kristin A. Altwegg
PY - 2026
DA - 2026/10/12
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1947958
UR - https://doi.org/10.3389/fonc.2026.1947958
AB - Obesity increases the risk and progression of at least 13 types of cancer. Although the epidemiologic links between excess adiposity and these cancers are well documented, the biological mechanisms linking obesity to carcinogenesis and tumor progression remain incompletely understood. White adipose tissue in obesity is a source of inflammatory and immunosuppressive signals that act systemically, driving metabolic, inflammatory, and immune dysfunction whose consequences differ across tumor types. As adipose tissue expands and adipocytes enlarge, the blood supply becomes inadequate, leading to hypoxia, fibrosis, lipolytic stress, macrophage recruitment, and chronic low-grade inflammation. These obesity-induced perturbations generate endocrine, cytokine, lipid, and metabolic signals that act systemically, within the tumor microenvironment (TME), and/or cell-intrinsically to activate oncogenic and tumor-promoting pathways. The same signals reshape innate and adaptive immunity, promoting tumor-permissive macrophage states and myeloid-derived suppressor cell expansion, while the effector arms weaken as antigen presentation, natural killer cell and T cell function all decline. This review synthesizes current evidence linking obesity-associated inflammation and immune dysregulation to cancer initiation, progression, and treatment responses across multiple obesity-related cancers. Emphasis is placed on adipose tissue inflammation, myeloid cell biology, T cell immunometabolism, endocrine-inflammatory crosstalk, and the relationship between obesity and immunotherapy. Finally, we discuss translational opportunities for preventing or intercepting obesity-related cancers, including weight loss achieved through lifestyle, surgical, or pharmacologic approaches, with an emphasis on GLP-1 receptor agonists given their substantial efficacy, rapid clinical uptake, and potential to reshape obesity-related cancer prevention and survivorship strategies. Defining the metabolic, immune, and inflammatory phenotypes that drive obesity-associated cancer risk and progression will be essential for developing more precise, mechanism-based strategies for prevention, treatment, and survivorship care.
SN - 2234-943X
ER -