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CD1d-restricted peripheral T cell lymphoma in mice and humans

Emmanuel Bachy 1 Mirjam Urb 1 Shilpi Chandra 2 Rémy Robinot 1 Gabriel Bricard 1 Simon de Bernard 3 Alexandra Traverse-Glehen 4 Sophie Gazzo 4 Olivier Blond 5 Archana Khurana 2 Lucile Baseggio 4 Tayla Heavican 6 Martine Ffrench 7, 8 Giuliano Crispatzu 9 Paul Mondière 1 Alexandra Schrader 9 Morgan Taillardet 1 Olivier Thaunat 1 Nadine Martin 10 Stéphane Dalle 11 Magali Le Garff-Tavernier 12 Gilles Salles 4 Joel Lachuer 11 Olivier Hermine 13, 14, 15 Vahid Asnafi 16 Mikael Roussel 17, 18 Thierry Lamy 18, 19 Marco Herling 9 Javeed Iqbal 6 Laurent Buffat 3 Patrice N. Marche 5 Philippe Gaulard 20, 10 Mitchell Kronenberg 2 Thierry Defrance 1 Laurent Genestier 1
Abstract : Peripheral T cell lymphomas (PTCLs) are a heterogeneous entity of neoplasms with poor prognosis, lack of effective therapies, and a largely unknown pathophysiology. Identifying the mechanism of lymphomagenesis and cell-of-origin from which PTCLs arise is crucial for the development of efficient treatment strategies. In addition to the well-described thymic lymphomas, we found that p53-deficient mice also developed mature PTCLs that did not originate from conventional T cells but from CD1d-restricted NKT cells. PTCLs showed phenotypic features of activated NKT cells, such as PD-1 up-regulation and loss of NK1.1 expression. Injections of heat-killedStreptococcus pneumonia, known to express glycolipid antigens activating NKT cells, increased the incidence of these PTCLs, whereasEscherichia coliinjection did not. Gene expression profile analyses indicated a significant down-regulation of genes in the TCR signaling pathway in PTCL, a common feature of chronically activated T cells. Targeting TCR signaling pathway in lymphoma cells, either with cyclosporine A or anti-CD1d blocking antibody, prolonged mice survival. Importantly, we identified human CD1d-restricted lymphoma cells within Vδ1 TCR-expressing PTCL. These results define a new subtype of PTCL and pave the way for the development of blocking anti-CD1d antibody for therapeutic purposes in humans
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Contributor : Laurent Jonchère <>
Submitted on : Thursday, April 21, 2016 - 10:41:50 AM
Last modification on : Thursday, July 22, 2021 - 10:10:02 AM

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Emmanuel Bachy, Mirjam Urb, Shilpi Chandra, Rémy Robinot, Gabriel Bricard, et al.. CD1d-restricted peripheral T cell lymphoma in mice and humans. Journal of Experimental Medicine, Rockefeller University Press, 2016, 213 (5), pp.841-57. ⟨10.1084/jem.20150794⟩. ⟨hal-01305487⟩



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