This chapter reviews the key properties of tumor-associated macrophages (TAMs), emphasizing on the genetic evidence and the emerging targets for therapeutic intervention. TAMs derive from the circulating monocytes and are recruited at the tumor site by a tumor-derived chemotactic factor for monocytes. TAMs that have immunoregulatory and immunosuppressive activity produce growth factors that stimulate angiogenesis, remodel tissues, and facilitate invasion and metastasis. TAMs and the related immature myeloid suppressor cells have the properties of M2 macrophage populations that are supportive to tumors. In many human tumors, a high frequency of infiltrating TAMs is associated with poor prognosis. TAMs participate in the proangiogenic process by producing the angiogenic factor thymidine phosphorylase (TP), which promotes the endothelial cell migration in vitro and whose levels of expression are associated with tumor neovascularization. TAMs contribute to tumor progression also by producing proangiogenic and tumor-inducing chemokines, such as CCL2. Moreover, TAMs accumulate in the hypoxic regions of tumors, and hypoxia triggers a proangiogenic program in these cells.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)