Obesity and melanoma: unraveling the paradoxical survival benefit in immunotherapy

Saginala, K., Barsouk, A., Aluru, J. S., Rawla, P. & Barsouk, A. (2021). Epidemiology of melanoma. Medical Science (Basel) 9. https://doi.org/10.3390/medsci9040063

Ferlay J, E. M., Lam, F., Laversanne, M., Colombet, M., Mery, L., Piñeros, M., Znaor, A., & Bray, I. S. F. (2024). Global cancer observatory: cancer today. Lyon, France: International Agency for Research on Cancer., <https://gco.iarc.who.int/today/>.

Siegel, R. L., Kratzer, T. B., Wagle, N. S., Sung, H., & Jemal, A. (2026). Cancer statistics, 2026. CA: A Cancer Journal for Clinicians, 76, Article e70043. https://doi.org/10.3322/caac.70043

Article  PubMed  PubMed Central  Google Scholar 

Wherry, E. J., & Kurachi, M. (2015). Molecular and cellular insights into T cell exhaustion. Nature Reviews Immunology, 15, 486–499. https://doi.org/10.1038/nri3862

Article  CAS  PubMed  PubMed Central  Google Scholar 

Barber, D. L., et al. (2006). Restoring function in exhausted CD8 T cells during chronic viral infection. Nature, 439, 682–687. https://doi.org/10.1038/nature04444

Article  CAS  PubMed  Google Scholar 

Blackburn, S. D., et al. (2009). Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nature Immunology, 10, 29–37. https://doi.org/10.1038/ni.1679

Article  CAS  PubMed  Google Scholar 

Velu, V., et al. (2009). Enhancing SIV-specific immunity in vivo by PD-1 blockade. Nature, 458, 206–210. https://doi.org/10.1038/nature07662

Article  CAS  PubMed  Google Scholar 

Twyman-Saint Victor, C., et al. (2015). Radiation and dual checkpoint blockade activate non-redundant immune mechanisms in cancer. Nature, 520, 373–377. https://doi.org/10.1038/nature14292

Article  CAS  PubMed  PubMed Central  Google Scholar 

Larkin, J., et al. (2019). Five-year survival with combined nivolumab and ipilimumab in advanced melanoma. The New England Journal of Medicine, 381, 1535–1546. https://doi.org/10.1056/NEJMoa1910836

Article  CAS  PubMed  Google Scholar 

Eggermont, A. M. M., et al. (2020). Longer follow-up confirms recurrence-free survival benefit of adjuvant pembrolizumab in high-risk stage III melanoma: Updated results from the EORTC 1325-MG/KEYNOTE-054 trial. Journal of Clinical Oncology, 38, 3925–3936. https://doi.org/10.1200/JCO.20.02110

Article  CAS  PubMed  PubMed Central  Google Scholar 

Weber, J., et al. (2017). Adjuvant nivolumab versus ipilimumab in resected stage III or IV melanoma. The New England Journal of Medicine, 377, 1824–1835. https://doi.org/10.1056/NEJMoa1709030

Article  CAS  PubMed  Google Scholar 

Robert, C., et al. (2023). Seven-year follow-up of the phase III KEYNOTE-006 study: Pembrolizumab versus ipilimumab in advanced melanoma. Journal of Clinical Oncology, 41, 3998–4003. https://doi.org/10.1200/JCO.22.01599

Article  CAS  PubMed  Google Scholar 

Larkin, J., et al. (2023). Adjuvant nivolumab versus ipilimumab in resected stage III/IV melanoma: 5-year efficacy and biomarker results from CheckMate 238. Clinical Cancer Research, 29, 3352–3361. https://doi.org/10.1158/1078-0432.CCR-22-3145

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ascierto, P. A., et al. (2020). Adjuvant nivolumab versus ipilimumab in resected stage IIIB-C and stage IV melanoma (CheckMate 238): 4-year results from a multicentre, double-blind, randomised, controlled, phase 3 trial. The Lancet Oncology, 21, 1465–1477. https://doi.org/10.1016/S1470-2045(20)30494-0

Article  CAS  PubMed  Google Scholar 

Cho, J., et al. (2016). Treatment outcome of PD-1 immune checkpoint inhibitor in Asian metastatic melanoma patients: Correlative analysis with PD-L1 immunohistochemistry. Investigational New Drugs, 34, 677–684. https://doi.org/10.1007/s10637-016-0373-4

Article  CAS  PubMed  Google Scholar 

Carlino, M. S., Larkin, J., & Long, G. V. (2021). Immune checkpoint inhibitors in melanoma. Lancet, 398, 1002–1014. https://doi.org/10.1016/S0140-6736(21)01206-X

Article  CAS  PubMed  Google Scholar 

Armstrong, B. K., & Kricker, A. (1993). How much melanoma is caused by sun exposure? Melanoma Research, 3, 395–402. https://doi.org/10.1097/00008390-199311000-00002

Article  CAS  PubMed  Google Scholar 

Elwood, J. M., & Gallagher, R. P. (1998). Body site distribution of cutaneous malignant melanoma in relationship to patterns of sun exposure. International Journal of Cancer, 78(3), 276–280. https://doi.org/10.1002/(sici)1097-0215(19981029)78:3%3c276::aid-ijc2%3e3.0.co;2-s

Article  CAS  PubMed  Google Scholar 

Hakimi, A. A., et al. (2013). An epidemiologic and genomic investigation into the obesity paradox in renal cell carcinoma. Journal of the National Cancer Institute, 105, 1862–1870. https://doi.org/10.1093/jnci/djt310

Article  CAS  PubMed  PubMed Central  Google Scholar 

McQuade, J. L., et al. (2018). Association of body-mass index and outcomes in patients with metastatic melanoma treated with targeted therapy, immunotherapy, or chemotherapy: A retrospective, multicohort analysis. The Lancet Oncology, 19, 310–322. https://doi.org/10.1016/S1470-2045(18)30078-0

Article  PubMed  PubMed Central  Google Scholar 

Guilbert, J. J. (2003). The world health report 2002 - Reducing risks, promoting healthy life. Education for Health (Abingdon), 16, 230. https://doi.org/10.1080/1357628031000116808

Article  CAS  Google Scholar 

(2000). Obesity: preventing and managing the global epidemic. Report of a WHO consultation. World Health Organ Tech Rep Ser 894, i-xii, 1–253

Wang, T., et al. (2016). Effects of obesity related genetic variations on visceral and subcutaneous fat distribution in a Chinese population. Scientific Reports, 6, Article 20691. https://doi.org/10.1038/srep20691

Article  CAS  PubMed  PubMed Central  Google Scholar 

Razak, F., et al. (2007). Defining obesity cut points in a multiethnic population. Circulation, 115, 2111–2118. https://doi.org/10.1161/CIRCULATIONAHA.106.635011

Article  PubMed  Google Scholar 

Delgado, C. (2025). Obesity: Can we cure our dependence on BMI? BMJ (Clinical Research Ed.), 389, Article r241. https://doi.org/10.1136/bmj.r241

Article  PubMed  Google Scholar 

Okorodudu, D. O., et al. (2010). Diagnostic performance of body mass index to identify obesity as defined by body adiposity: A systematic review and meta-analysis. International Journal of Obesity (London, England : 2005), 34, 791–799. https://doi.org/10.1038/ijo.2010.5

Article  CAS  Google Scholar 

Bandera, E. V., et al. (2016). The use and interpretation of anthropometric measures in cancer epidemiology: A perspective from the world cancer research fund international continuous update project. International Journal of Cancer, 139, 2391–2397. https://doi.org/10.1002/ijc.30248

Article  CAS  PubMed  Google Scholar 

McQuade, J. L., Daniel, C. R., & Davies, M. A. (2018). Body-mass index and metastatic melanoma outcomes - Authors’ reply. Lancet Oncology, 19, e227–e228. https://doi.org/10.1016/S1470-2045(18)30266-3

Article  PubMed  Google Scholar 

Romero-Corral, A., et al. (2008). Accuracy of body mass index in diagnosing obesity in the adult general population. International Journal of Obesity (London), 32, 959–966. https://doi.org/10.1038/ijo.2008.11

Article  CAS  Google Scholar 

Shah, N. R., & Braverman, E. R. (2012). Measuring adiposity in patients: The utility of body mass index (BMI), percent body fat, and leptin. PLoS ONE, 7, Article e33308. https://doi.org/10.1371/journal.pone.0033308

Article  CAS  PubMed  PubMed Central  Google Scholar 

Arnold, M., et al. (2016). Duration of adulthood overweight, obesity, and cancer risk in the Women’s Health Initiative: A longitudinal study from the United States. PLoS Medicine, 13, Article e1002081.

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