DESCRIPTION:

Obesity has been established as a leading risk factor for many cancers and can drive tumor progression and metastasis. Paradoxically, obesity has in some cases been associated with better survival and improved response to immune checkpoint blockade therapies. The role of the immune system in the obesity-cancer connection and how obesity affects immunotherapy responses, however, have been unclear. Here we report that diet induced obesity in mice induces macrophage PD-1 upregulation to promote tumor growth while potentiating immunotherapy responses. These findings identify PD-1 as a metabolic regulator in TAM dysfunction and reveal a unique PD-1 mediated and macrophage-specific mechanism for immune tumor surveillance and checkpoint blockade. This may contribute to improved immunotherapy response in TAM-enriched tumors and obesity.

LEARNING OBJECTIVES

At the conclusion of this activity, participants will be able to:

• Understand the paradoxical role of macrophages in obesity associated cancers
• Appreciate that immune checkpoint blockade therapy can target macrophages in addition to T cells.