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TGFß, a Potent Regulator of Tumor Microenvironment and Host Immune Response, Implication for Therapy

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Alterations in TGFß signaling are common in human cancers. TGFß has significant impact on tumor initiation and progression. Therapeutic strategies including neutralizing antibodies and small molecular inhibitors have been developed to target TGFß signaling. However, TGFß can work as both a tumor suppressor and a tumor promoter. A significant challenge to the development of successful TGFß antagonism treatment is understanding how and when TGFß switches its function from a tumor suppressor to a tumor promoter. Recent studies demonstrate that TGFß regulates the infiltration of inflammatory cells and cancer associated fibroblasts into the tumor microenvironment, resulting in changes in signaling cascade in tumor cells. Additionally, TGFß exerts systemic immune suppression and significantly inhibits host tumor immune surveillance. Neutralizing TGFß in preclinical mouse models enhances CD8+ T-cell and natural killer cell-mediated anti-tumor immune response. This new understanding of TGFß signaling in regulation of tumor microenvironment and immune response may provide useful information, particularly for patient selection and inflammation/immune biomarkers for TGFß antagonism therapy in clinical trials.

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Keywords: TGFß; antagonism; bone marrow; breast tumor; inflammation; metastasis; myeloid cells; tumor microenvironment

Document Type: Research Article

Publication date: June 1, 2010

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  • Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal will invite guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.
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