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]

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

Domains: Life Sciences [q-bio]

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, 2016, 213 (5), pp.841-57. ⟨10.1084/jem.20150794⟩. ⟨hal-01305487⟩