TGFbeta, a potent regulator of tumor microenvironment and host immune response, implication for therapy.
Alterations in TGFbeta signaling are common in human cancers. TGFbeta has significant impact on tumor initiation and progression. Therapeutic strategies including neutralizing antibodies and small molecular inhibitors have been developed to target TGFbeta signaling. However, TGFbeta can work as both a tumor suppressor and a tumor promoter. A significant challenge to the development of successful TGFbeta antagonism treatment is understanding how and when TGFbeta switches its function from a tumor suppressor to a tumor promoter. Recent studies demonstrate that TGFbeta regulates the infiltration of inflammatory cells and cancer associated fibroblasts into the tumor microenvironment, resulting in changes in signaling cascade in tumor cells. Additionally, TGFbeta exerts systemic immune suppression and significantly inhibits host tumor immune surveillance. Neutralizing TGFbeta in preclinical mouse models enhances CD8+ T-cell and natural killer cell-mediated anti-tumor immune response. This new understanding of TGFbeta signaling in regulation of tumor microenvironment and immune response may provide useful information, particularly for patient selection and inflammation/immune biomarkers for TGFbeta antagonism therapy in clinical trials.
Yang
L
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Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20876-4258, USA. yangl@mail.nih.gov
D000818:Animals; D002273:Carcinogens / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D008954:Models, Biological; D009362:Neoplasm Metastasis / Q000276:immunology / Q000503:physiopathology; D009369:Neoplasms / Q000276:immunology* / Q000503:physiopathology* / Q000628:therapy; D015398:Signal Transduction; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000276:immunology / Q000502:physiology
D002273:Carcinogens; D016212:Transforming Growth Factor beta; D025521:Tumor Suppressor Proteins