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IFNγ Receptor-STAT1 Signaling and Cancer Immunoediting

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Signal Transducers and Activators of Transcription (STATs)

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Abstract

Investigations from many different laboratories on the contributions of the JAK-STAT signaling pathway to oncogenesis have suggested a general categorization of the STAT molecules as either tumor suppressors or tumor promoters. In this regard, STAT1 can be broadly defined as a tumor suppressor whereas STAT3, STAT5 and STAT6 can be classified as tumor promoters. In this review, we focus primarily on recent contributions from our laboratory and others regarding the existence of an extrinsic tumor suppressor system that involves interferon-gamma (IFNγ), STAT1 and lymphocytes. First, we describe the experimental path that led us to investigate a role for IFNγ and its STAT1 signaling pathway in promoting natural host responses against cancer before summarizing our findings that the IFNγ/STAT1 axis functions as the basis of an extrinsic tumor suppressor system. Second, we discuss possible mechanisms by which STAT1 exerts its tumor suppressor effects. Finally, we incorporate these observations into the much debated hypothesis of cancer immunosurveillance and bring closure to this 100 year old controversy by introducing a refined concept of immunosurveillance we have termed Cancer Immunoediting.

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Author information

Authors and Affiliations

  1. Washington University School of Medicine, St. Louis, MO, 63110, USA

    Ravindra Uppaluri, Gavin P. Dunn & Robert D. Schreiber

  2. Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York, NY, 10021, USA

    Lloyd J. Old

Authors
  1. Ravindra Uppaluri
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  2. Gavin P. Dunn
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  3. Lloyd J. Old
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  4. Robert D. Schreiber
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Editor information

Editors and Affiliations

  1. New York University School of Medicine, USA

    Pravin B. Sehgal  & David E. Levy  & 

  2. Osaka University, Japan

    Toshio Hirano

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Uppaluri, R., Dunn, G.P., Old, L.J., Schreiber, R.D. (2003). IFNγ Receptor-STAT1 Signaling and Cancer Immunoediting. In: Sehgal, P.B., Levy, D.E., Hirano, T. (eds) Signal Transducers and Activators of Transcription (STATs). Springer, Dordrecht. https://doi.org/10.1007/978-94-017-3000-6_27

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  • DOI: https://doi.org/10.1007/978-94-017-3000-6_27

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-90-481-6421-9

  • Online ISBN: 978-94-017-3000-6

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