Macrophages, Innate Immunity and Cancer: Balance, Tolerance, and Diversity

Smouldering inflammation is a component of the tumor microenvironment and represents the 7(th) hallmark of cancer. Tumor-associated macrophages (TAM) have served as a paradigm for cancer promoting inflammation. Tumor-associated macrophages orchestrate various aspects of cancer, including: diversion and skewing of adaptive responses; cell growth; angiogenesis; matrix deposition and remodelling; the construction of a metastatic niche and actual metastasis; response to hormones and chemotherapeutic agents. T and B cells or cancer cell-derived signals orchestrate the functional reprogramming of TAM. In general TAM acquire M2-like properties and resemble 'tolerant' macrophages, though there is diversity in pathways and phenotypes in different tumors. TAM can also express antitumor activity. Thus, in response to microenvironmental signals, TAM can exert dual influence on tumor growth and progression.