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Obesity-driven metabolic reprogramming and immune dysfunction in renal cancer
Henry N Ogbonna1,2, Lyse A Norian2,3
1Graduate Biomedical Sciences, Pathology, Pharmacology, and Physiology Theme, University of Alabama at Birmingham, Birmingham, AL, United States.
Frontiers in Immunology
|June 29, 2026
Summary
Obesity significantly impacts clear cell renal cell carcinoma (ccRCC) by altering the tumor microenvironment and immune response. Understanding these immunometabolic changes is crucial for developing effective ccRCC treatments.
Area of Science:
- Oncology
- Immunology
- Metabolism
Background:
- Clear cell renal cell carcinoma (ccRCC) is a metabolic tumor where host physiology influences progression and treatment resistance.
- Obesity is a major risk factor for RCC, profoundly altering the tumor microenvironment beyond simple fat accumulation.
Purpose of the Study:
- To summarize current knowledge on obesity-driven immunometabolic rewiring in ccRCC.
- To outline key priorities for future research, including preclinical models, biomarkers, and clinical trials.
Main Methods:
- Review of current literature on obesity, ccRCC, and immunometabolism.
- Analysis of how obesity-induced factors (adipokines, cytokines) interact with ccRCC cell metabolism and immune cells.
Main Results:
- Obesity promotes ccRCC growth and immunosuppression via metabolic rewiring, inflammation, altered vasculature, and immune cell dysfunction.
- Specific factors like leptin, resistin, IL-6, and VEGF increase, while adiponectin decreases, driving angiogenesis and immune evasion.
- Obesity reshapes the immune landscape by recruiting myeloid-derived suppressor cells (MDSCs), polarizing tumor-associated macrophages (TAMs), and impairing dendritic cells (DCs) and T cells.
Conclusions:
- Obesity-driven immunometabolic alterations are central to ccRCC progression and therapeutic resistance.
- The 'obesity paradox' in RCC outcomes may be influenced by limitations of BMI and variations in inflammation and body composition.
- Future research should focus on obesity-relevant models, biomarkers of adiposity and inflammation, and immunometabolism-targeted therapies.
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