McQuade et al.¹ have recently reported that in male patients with metastatic melanoma, obesity at the onset of systemic treatment (targeted and immunotherapy) is not only associated with increased progression-free survival but also with improved overall survival when compared to patients with a normal body mass index (BMI). On the basis of these results the authors called for further research to confirm the association and investigate the potential mechanisms which underlie it. To this end, we would like to highlight one potentially important mechanism; the gut microbiome. Indeed several recent publications have reported that the gut microbiome may influence response to immune checkpoint therapy,^2,3 potentially improving treatment efficacy, and may predict which patients are at risk of developing potentially life-threatening side effects, including immune-mediated colitis.⁴ In fact, the clinical efficacy of immunotherapy, specifically anti-CTLA-4 therapy, may depend on the composition of the gut bacteria flora in order to exert their anti-tumor effect.⁵ This article is protected by copyright. All rights reserved.