Macrophages and NF-κB in cancer.

Curr Top Microbiol Immunol (2011) PMID 21080151

Macrophages are tissue resident phagocytes with important roles in development, wound healing, and inflammation. There is enormous heterogeneity in macrophage phenotype, from 'classically' activated macrophages that have important roles in inflammation and innate immunity, to 'alternative' macrophage activation that is associated with wound healing, angiogenesis, and immune-suppression. Most, if not all, solid tumors have a significant macrophage population, clinical and experimental evidence suggests tumor-associated macrophages (TAM) are linked with tumor progression. The trophic functions of TAM are associated with increased angiogenesis, malignant cell invasion, and metastasis. NF-κB is s central regulator of inflammation and NF-κB activation particularly in TAM is linked with promotion of carcinogenesis in various experimental models of inflammation-associated cancer. NF-κB activation in TAM has, therefore, been suggested to represent a molecular link between inflammation and cancer. However, TAM frequently display an anti-inflammatory phenotype linked with immune-suppression that is not easily reconciled with a pro-inflammatory function for NF-κB in TAM. Here, I review the form and function of TAM and discuss the role of NF-κB activation in TAM in carcinogenesis.