The Influence of Obesity on Outcomes with Immune Checkpoint Blockade: Clinical Evidence and Potential Biological Mechanisms

Authors

Andrew W Hahn
Neha Venkatesh
Pavlos Msaouel
Jennifer L McQuade

Publication Date

10-31-2023

Journal

Cells

Abstract

Immune checkpoint blockade (ICB) is a mainstay of treatment for advanced cancer, yet tumor response and host toxicity are heterogenous in those patients who receive ICB. There is growing interest in understanding how host factors interact with tumor intrinsic properties and the tumor microenvironment to influence the therapeutic index with ICB. Obesity, defined by body mass index, is a host factor associated with improved outcomes in select cancers when treated with ICB. While the biological mechanism for this obesity paradox is not fully understood, pre-clinical and translational studies suggest obesity may potentially impact tumor metabolism, inflammation, and angiogenesis. Herein, we summarize clinical studies that support an obesity paradox with ICB, explore potential biological mechanisms that may account for the obesity paradox, and address methodological challenges to consider when studying obesity and treatment outcomes.

Keywords

Humans, Immune Checkpoint Inhibitors, Neoplasms, Obesity, Inflammation, Tumor Microenvironment, body composition, immunotherapy, melanoma, obesity, renal cell carcinoma.

DOI

10.3390/cells12212551

PMID

37947629

PMCID

PMC10649394

PubMedCentral® Posted Date

10-31-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes