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Perturbations of TGF-β Signaling in Leukocytes as Drivers of Leukemogenesis and Epithelial Tumorigenesis

  • Chapter
Transforming Growth Factor-β in Cancer Therapy, Volume II

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

The inactivation of specific components of the transforming growth factor-beta (TGF-β) signaling pathway has been implicated in many types of hematological malignancies. These range from alterations at the level of TGF-β receptors to mutations, deletions or functional inactivation of downstream signaling components such as members of the Smad family of proteins. It is becoming increasingly apparent that, in addition to playing a role in the progression of certain leukemias, disruption of TGF-β signaling in the lymphoid compartment also has profound effects on tumor progression of epithelial cells. In this respect, the use of conditional knockout murine models has been particularly instructive. We review here well-documented examples where TGF-β signaling is thought to control leukemogenesis. More recent data from our laboratory and others are lighlighted in support of a role for T-cell TGF-β signaling in regulating epithelial tumor progression. Finally, we review the link between TGF-β, regulatory T cells (Treg) and tumor immunotherapies, an understanding of which has significant therapeutic relevance.

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Authors and Affiliations

  1. MaxCyte, Inc., Gaithersburg, MD, USA

    Lawrence A. Wolfraim PhD

  2. Pediatric Hematology/Oncology, Rainbow Babies & Children’s Hospital, Case Western Reserve University, Cleveland, OH, USA

    John J. Letterio MD, PhD

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  1. Lawrence A. Wolfraim PhD
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  1. Cancer Training Branch, Office of Centers, Training and Resources, National Cancer Institute, Bethesda, MD

    Sonia B. Jakowlew PhD

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Wolfraim, L.A., Letterio, J.J. (2008). Perturbations of TGF-β Signaling in Leukocytes as Drivers of Leukemogenesis and Epithelial Tumorigenesis. In: Jakowlew, S.B. (eds) Transforming Growth Factor-β in Cancer Therapy, Volume II. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-293-9_13

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