Tumor-associated macrophages, multi-tasking cells in the cancer landscape

It is now well recognized that myeloid cells of the innate immunity infiltrating the tumor micro-environment, instead of halting tumor progression, favour the proliferation of tumor cells and their invasive ability. In particular, macrophages represent the most abundant leukocyte population recruited at tumor sites, from early stages till the occurrence of metastasis. Tumor-Associated Macrophages (TAMs) are crucial determinants of cancer cell survival and proliferation; they efficiently trigger neo-angiogenesis and matrix degradation and suppress potential anti-tumor adaptive immune responses. Established evidence demonstrated that high density of infiltrating TAMs is usually associated with fast tumor progression and resistance to anti-cancer therapies. Targeting of TAMs or modulation of their functions is now actively pursued. In this review we discuss recent knowledge and current therapeutic approaches behind TAMs. A better understanding of their features, heterogeneity in particular, and of their tumor-promoting functions is essential to better design TAM-centered therapeutic interventions. Understanding of how best to combine TAM-targeted approaches and conventional chemotherapy or immunotherapy, holds promise for successful anti-cancer treatments.