TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression.

ABSTRACT

Transforming growth factor beta (TGF-beta) plays an important role in tumor initiation and progression, functioning as both a suppressor and a promoter. The mechanisms underlying this dual role of TGF-beta remain unclear. TGF-beta exerts systemic immune suppression and inhibits host immunosurveillance. Neutralizing TGF-beta enhances CD8+ T-cell- and NK-cell-mediated anti-tumor immune responses. It also increases neutrophil-attracting chemokines resulting in recruitment and activation of neutrophils with an antitumor phenotype. In addition to its systemic effects, TGF-beta regulates infiltration of inflammatory/immune cells and cancer-associated fibroblasts in the tumor microenvironment causing direct changes in tumor cells. Understanding TGF-beta regulation at the interface of tumor and host immunity should provide insights into developing effective TGF-beta antagonists and biomarkers for patient selection and efficacy of TGF-beta antagonist treatment.