title: T-cell receptor signaling in peripheral T-cell lymphoma - a review of patterns of alterations in a central growth regulatory pathway.
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.
authors.affiliation: Laboratory for Lymphocyte Signaling and Oncoproteome, Department I of Internal Medicine, Center for Integrated Oncology Köln-Bonn, Cologne, Germany.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Warner
authors.forename: Nicole
authors.initials: N
authors.lastname: Weit
authors.forename: Giuliano
authors.initials: G
authors.lastname: Crispatzu
authors.forename: Joan
authors.initials: J
authors.lastname: Admirand
authors.forename: Dan
authors.initials: D
authors.lastname: Jones
authors.forename: Marco
authors.initials: M
authors.lastname: Herling
mesh_terms: D002471:Cell Transformation, Neoplastic; D006801:Humans; D016411:Lymphoma, T-Cell, Peripheral / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D011948:Receptors, Antigen, T-Cell
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