Wnt signaling in the phenotype and function of tumor-associated macrophages.

Tumor-associated macrophages (TAM) play an important role in supporting tumor growth and suppressing anti-tumor immune responses, and TAM infiltration has been associated with poor patient prognosis in various cancers. TAMs can be classified as pro-inflammatory, M1-like, or anti-inflammatory, M2-like. While multiple factors within the tumor microenvironment affect the recruitment, polarization, and functions of TAMs, accumulating evidence suggests that Wnt signaling represents an important, targetable driver of an immunosuppressive, M2-like TAM phenotype. TAM production of Wnt ligands mediates TAM-tumor crosstalk to support cancer cell proliferation, invasion, and metastasis. Targeting TAM polarization and the pro-tumorigenic functions of TAMs through inhibitors of Wnt signaling may prove a beneficial treatment strategy in cancers where macrophages are prevalent in the microenvironment.