Role of tumour-associated macrophages in cancer-related inflammation

The construction of an inflammatory microenvironment provides the fuel for cancer development and progression. Hence, solid tumors promote infiltration of leukocyte populations, among which tumor-associated macrophages (TAM) represent a paradigm for cancer promoting inflammation. TAM orchestrate various aspects of cancer, including diversion and skewing of adaptive responses, cell growth, angiogenesis, matrix deposition and remodeling, the construction of a metastatic niche and actual metastasis, response to hormones and chemotherapeutic agents. Several evidence indicate that TAM show a remarkable degree of plasticity and functional heterogeneity, suggesting that during tumor progression macrophages undergo a phenotypic 'switch', eventually exhibiting the alternatively activated, 'M2', phenotype, associated with immunosuppression, promotion of tumor angiogenesis and metastasis. While recent studies have attempted to address the role of microenvironment signals on the TAM « reprogramming», the interplay between innate and adaptive immunity is emerging as a crucial step of this event. Here I discuss the evidence for the functional reprogramming of TAM during the course of tumor progression and the molecular mechanisms that regulate such event. Finally, I discuss the implications of this phenomenon for anti-cancer therapies aimed at prompting TAM to mount an effective antitumor response.