Therapeutic Approaches Targeting Proteins in Tumor-Associated Macrophages and Their Applications in Cancers

Tumor-associated macrophages (TAMs) promote tumor proliferation, invasion, angiogenesis, stemness, therapeutic resistance, and immune tolerance in a protein-dependent manner. Therefore, the traditional target paradigms are often insufficient to exterminate tumor cells. These pro-tumoral functions are mediated by the subsets of macrophages that exhibit canonical protein markers, while simultaneously having unique transcriptional features, which makes the proteins expressed on TAMs promising targets during anti-tumor therapy. Herein, TAM-associated protein-dependent target strategies were developed with the aim of either reducing the numbers of TAMs or inhibiting the pro-tumoral functions of TAMs. Furthermore, the recent advances in TAMs associated with tumor metabolism and immunity were extensively exploited to repolarize these TAMs to become anti-tumor elements and reverse the immunosuppressive tumor microenvironment. In this review, we systematically summarize these current studies to fully illustrate the TAM-associated protein targets and their inhibitors, and we highlight the potential clinical applications of targeting the crosstalk among TAMs, tumor cells, and immune cells in anti-tumor therapy.