T-cell receptor signaling in peripheral T-cell lymphoma - A review of patterns of alterations in a central growth regulatory pathway

Kathrin Warner, Nicole Weit, Giuliano Crispatzu, Joan Admirand, Dan Jones, Marco Herling

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)163-172
Number of pages10
JournalCurrent Hematologic Malignancy Reports
Volume8
Issue number3
DOIs
StatePublished - Sep 1 2013

Fingerprint

Peripheral T-Cell Lymphoma
T-Cell Antigen Receptor
Growth
T-Cell Leukemia
Neoplasms
Autoantigens
Cellular Structures
Epidemiology
T-Lymphocytes
Antigens

Keywords

  • Anaplastic large cell lymphoma (ALCL)
  • Mature T-cell lymphoma/leukemia
  • Peripheral T-cell lymphoma (PTCL)
  • T-cell homeostasis
  • T-cell prolymphocytic leukemia (T-PLL)
  • T-cell receptor (TCR)

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

T-cell receptor signaling in peripheral T-cell lymphoma - A review of patterns of alterations in a central growth regulatory pathway. / Warner, Kathrin; Weit, Nicole; Crispatzu, Giuliano; Admirand, Joan; Jones, Dan; Herling, Marco.

In: Current Hematologic Malignancy Reports, Vol. 8, No. 3, 01.09.2013, p. 163-172.

Research output: Contribution to journalArticle

Warner, Kathrin ; Weit, Nicole ; Crispatzu, Giuliano ; Admirand, Joan ; Jones, Dan ; Herling, Marco. / T-cell receptor signaling in peripheral T-cell lymphoma - A review of patterns of alterations in a central growth regulatory pathway. In: Current Hematologic Malignancy Reports. 2013 ; Vol. 8, No. 3. pp. 163-172.
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