TGF-beta and immune cells: an important regulatory axis in the tumor microenvironment and progression.
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.
Yang
Li
L
Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20876, USA. yangl3@mail.nih.gov
Pang
Yanli
Y
Moses
Harold L
HL
D000818:Animals; D018450:Disease Progression; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism
D016212:Transforming Growth Factor beta