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)
1
Lymphocytes B effecteurs et à mémoire – Effector and memory B cells
2 La Jolla Institute for Immunology [La Jolla, CA, États-Unis]
3 AltraBio [Lyon]
4 LBMC UMR 5239 - Laboratoire de biologie et modélisation de la cellule
5 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
6 University of Nebraska Medical Center
7 Laboratoire d'Hématologie Cellulaire
8 LBMC - Laboratoire de Biologie Moléculaire de la Cellule
9 University of Cologne
10 IMRB - Institut Mondor de Recherche Biomédicale
11 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
12 CRC - Centre de Recherche des Cordeliers
13 CEREMAST - Centre de référence des mastocytoses
14 Service d'Hématologie Adulte
15 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
16 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
17 Laboratoire d'Hematologie
18 MiCa - Microenvironnement et cancer
19 CHU Pontchaillou [Rennes]
20 Département de pathologie [Mondor]
2 La Jolla Institute for Immunology [La Jolla, CA, États-Unis]
3 AltraBio [Lyon]
4 LBMC UMR 5239 - Laboratoire de biologie et modélisation de la cellule
5 INSERM U823 - Institut d'oncologie/développement Albert Bonniot de Grenoble
6 University of Nebraska Medical Center
7 Laboratoire d'Hématologie Cellulaire
8 LBMC - Laboratoire de Biologie Moléculaire de la Cellule
9 University of Cologne
10 IMRB - Institut Mondor de Recherche Biomédicale
11 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
12 CRC - Centre de Recherche des Cordeliers
13 CEREMAST - Centre de référence des mastocytoses
14 Service d'Hématologie Adulte
15 IMAGINE - U1163 - Imagine - Institut des maladies génétiques
16 INEM - UM 111 (UMR 8253 / U1151) - Institut Necker Enfants-Malades
17 Laboratoire d'Hematologie
18 MiCa - Microenvironnement et cancer
19 CHU Pontchaillou [Rennes]
20 Département de pathologie [Mondor]
Emmanuel Bachy
- Function : Author
- PersonId : 981999
Rémy Robinot
- Function : Author
- PersonId : 777780
- ORCID : 0000-0002-3651-0171
Olivier Thaunat
- Function : Author
- PersonId : 768194
- ORCID : 0000-0002-3648-8963
- IdRef : 074257544
Nadine Martin
- Function : Author
- PersonId : 773450
- ORCID : 0000-0002-4806-2388
Gilles Salles
- Function : Author
- PersonId : 765692
- ORCID : 0000-0002-9541-8666
- IdRef : 067204236
Olivier Hermine
- Function : Author
- PersonId : 756140
- ORCID : 0000-0003-2574-3874
- IdRef : 069884927
Mikael Roussel
- Function : Author
- PersonId : 182555
- IdHAL : mikael-roussel
- ORCID : 0000-0002-9741-0668
- IdRef : 074631330
Patrice N. Marche
- Function : Author
- PersonId : 176853
- IdHAL : patrice-n-marche
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