Adiponectin and its receptor signaling: an anti-cancer therapeutic target and its implications for anti-tumor immunity.

INTRODUCTION: Adiponectin (APN), produced by adipocytes, has direct anti-diabetic, anti-atherogenic and anti-inflammatory properties. Circulating APN levels are lower in obesity, a disease state that is often associated with several malignancies. AREA COVERED: Increasingly, clinical data suggests that serum APN may have an important protective role in carcinogenesis. Certain cancer cell types express APN receptors and their downstream signaling pathways may influence cancer biology, possibly by regulating cell proliferation and inducing apoptosis. However, APN's role in the immune system, in particular to the anti-tumor response, remains elusive. Therefore, this review critically addresses all controversies associated with the effect of APN on the immune system. EXPERT OPINION: Currently, the promise of interfering with APN and its receptor axis as a novel anti-cancer therapeutic target is rather encouraging. Greater understanding of the immunological side effects following this interference is crucial for the development of effective therapeutic strategies against obesity-associated malignancies. APN receptor signaling on immune cells can blunt anti-tumor immunity and induce tumor-specific tolerance. This may also have far-reaching consequences on the application of APN as an anti-cancer agent.