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T-Cell Receptor Signaling in Peripheral T-Cell Lymphoma – A Review of Patterns of Alterations in a Central Growth Regulatory Pathway

  • Lymphomas (C Dearden, Section Editor)
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Abstract

T-cell receptor (TCR) signaling is pivotal in T-cell development and function. In peripheral T-cell lymphomas/leukemias (PTCL/L), histogenesis, transforming events, epidemiology, and clinical presentation are also closely linked to TCR-mediated influences. After reviewing the physiology of normal TCR signaling and cellular responses, we describe here the association of subgroups of PTCL/L with specific patterns of TCR activation as relevant tumor-initiating and/or tumor-sustaining programs. We identify PTCL/L with a functionally intact TCR machinery in which stimulation is possibly incited by exogenous antigens or autoantigens. Distinct from these are tumors with autonomous oncogenic signaling by dysregulated TCR components uncoupled from extrinsic receptor input. A further subset is characterized by transforming events that activate molecules acting as substitutes for TCR signaling, but triggering similar downstream cascades. We finally discuss the consequences of such a functional model for TCR-targeted therapeutic strategies including those that are being tested in the clinic and those that still require further development.

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Acknowledgments

Support of relevance to this manuscript: Work on the biology of T-PLL by M.H. and N.W. has been awarded for continuation by a grant of the German José Carreras Leukemia Foundation. M.H. is funded by the German Research Foundation (DFG) under HE-3553/4-1 as part of the FOR-1961 collaborative research group ‘CONTROL-T’.

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Conflicts of Interest

Kathrin Warner declares that she has no conflict of interest.

Nicole Weit has been employed by Beckman Coulter GmbH since 2012.

Giuliano Crispatzu declares that he has no conflict of interest.

Joan Admirand declares that she has no conflict of interest.

Dan Jones works at Quest Diagnostics and has received research grants from NIH, and royalties from MD Anderson Cancer Center.

Marco Herling declares that he has no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Authors and Affiliations

  1. Laboratory for Lymphocyte Signaling and Oncoproteome, Department I of Internal Medicine, Center for Integrated Oncology Köln-Bonn, and Cologne Cluster of Excellence in Cellular Stress Responses in Aging-associated Diseases (CECAD), University of Cologne, Cologne, Germany

    Kathrin Warner, Nicole Weit, Giuliano Crispatzu & Marco Herling

  2. Clinical Pathology Associates, Austin, TX, USA

    Joan Admirand

  3. School of Health Professions, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    Dan Jones

  4. Laboratory for Lymphocyte Signaling and Oncoproteome, Department of Internal Medicine I, University Hospital Cologne, LFI Building, Level 4, Room 701, Kerpener Str. 62, 50937, Cologne, Germany

    Marco Herling

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  1. Kathrin Warner
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  2. Nicole Weit
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  3. Giuliano Crispatzu
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  4. Joan Admirand
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Correspondence to Marco Herling.

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Warner, K., Weit, N., Crispatzu, G. et al. T-Cell Receptor Signaling in Peripheral T-Cell Lymphoma – A Review of Patterns of Alterations in a Central Growth Regulatory Pathway. Curr Hematol Malig Rep 8, 163–172 (2013). https://doi.org/10.1007/s11899-013-0165-2

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