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 antitumor 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 microenvi-ronment affect the recruitment, polarization, and functions of TAMs, accumulating evidence suggests that Wnt signaling represents an important, targetable driver of an immunosup-pressive, M2-like TAM phenotype. TAM production of Wnt ligands mediates TAM-tumor cross-talk to support cancer cell proliferation, invasion, and metastasis. Targeting TAM polar-ization and the protumorigenic functions of TAMs through inhibitors of Wnt signaling may prove a beneficial treatment strategy in cancers where macrophages are prevalent in the microenvironment.

Automated summary

Tumor-associated macrophages (TAM) have a significant impact on tumor growth and immune responses, with TAM infiltration being linked to poor prognosis in various cancers. TAMs can be categorized as pro-inflammatory, M1-like, or anti-inflammatory, M2-like. Recent evidence suggests that Wnt signaling plays a crucial role in promoting an immunosuppressive, M2-like phenotype in TAMs, facilitating cancer cell proliferation, invasion, and metastasis. Targeting TAM polarization and their protumorigenic functions through Wnt signaling inhibitors could potentially be an effective treatment strategy in cancers with a high presence of macrophages in the microenvironment.