Pan-tumor analysis of the obesity paradox in immune checkpoint blockade

Obesity is a risk factor for developing cancer but is also associated with improved outcomes after treatment with immune checkpoint inhibitors, as was confirmed in a prospective study of patients with advanced or metastatic solid tumors at Johns Hopkins University (Baltimore, MD). To explain this obesity paradox, the authors collected serial peripheral blood samples for evaluation of concentration of 37 cytokines and immune cell clusters. Obese patients had lower serum IL-15 levels at baseline and lower on-treatment levels of IL-6, IL-8, and IL-15. Low on-treatment levels of IL-6 (HR 0.27; p=0.03) and IL-8 (HR 0.19; p=0.01) were associated with improved overall survival. Obese patients demonstrated lower levels of T effector cells with reduced expression of cytotoxicity markers and higher expression of exhaustion markers at baseline and on-treatment. The authors conclude that obese compared with non-obese patients with cancer have divergent immunological responses to ICIs.