Exploiting the obesity-associated immune microenvironment for cancer therapeutics

Obesity causes chronic low-grade inflammation and leads to changes in the immune landscape of multiple organ systems. Given the link between chronic inflammatory conditions and cancer, it is not surprising that obesity is associated with increased risk and worse outcomes in many malignancies. Paradoxically, recent epidemiological studies have shown that high BMI is associated with increased efficacy of immune checkpoint inhibitors (ICI), and a causal relationship has been demonstrated in the preclinical setting. It has been proposed that obesity-associated immune dysregulation underlies this observation by inadvertently creating a favourable microenvironment for increased ICI efficacy. The recent success of ICIs in obese cancer patients raises the possibility that additional immune-targeted therapies may hold therapeutic value in this context. Here we review how obesity affects the immunological composition of the tumor microenvironment in ways that can be exploited for cancer immunotherapies. We discuss existing literature supporting a beneficial role for obesity during ICI therapy in cancer patients, potential opportunities for targeting the innate immune system to mitigate chronic inflammatory processes, and how to pinpoint obese patients who are most likely to benefit from immune interventions without relying solely on body mass index. Given that the incidence of obesity is expanding on an international scale, we propose that understanding obesity-associated inflammation is necessary to reduce cancer mortalities and capitalize on novel therapeutic opportunities in the era of cancer immunotherapy. (C) 2021 Published by Elsevier Inc.