000223214 001__ 223214
000223214 005__ 20181203024441.0
000223214 0247_ $$2doi$$a10.1016/j.cell.2016.08.032
000223214 022__ $$a0092-8674
000223214 02470 $$2ISI$$a000386343100017
000223214 037__ $$aARTICLE
000223214 245__ $$aLoss of the HVEM Tumor Suppressor in Lymphoma and Restoration by Modified CAR-T Cells
000223214 260__ $$bCell Press$$c2016$$aCambridge
000223214 269__ $$a2016
000223214 300__ $$a27
000223214 336__ $$aJournal Articles
000223214 520__ $$aThe HVEM (TNFRSF14) receptor gene is among the most frequently mutated genes in germinal center lymphomas. We report that loss of HVEM leads to cell-autonomous activation of B cell proliferation and drives the development of GC lymphomas in vivo. HVEM-deficient lymphoma B cells also induce a tumor-supportive microenvironment marked by exacerbated lymphoid stroma activation and increased recruitment of T follicular helper (T-FH) cells. These changes result from the disruption of inhibitory cell-cell interactions between the HVEM and BTLA (B and T lymphocyte attenuator) receptors. Accordingly, administration of the HVEM ectodomain protein (solHVEM ((P37-V202))) binds BTLA and restores tumor suppression. To deliver solHVEM to lymphomas in vivo, we engineered CD19-targeted chimeric antigen receptor (CAR) T cells that produce solHVEM locally and continuously. These modified CAR-T cells show enhanced therapeutic activity against xenografted lymphomas. Hence, the HVEM-BTLA axis opposes lymphoma development, and our study illustrates the use of CAR-T cells as "micro-pharmacies'' able to deliver an anti-cancer protein.
000223214 700__ $$uMem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA$$aBoice, Michael
000223214 700__ $$aSalloum, Darin
000223214 700__ $$uUniv Rennes 1, EFS Bretagne, CHU Rennes, Equipe Labellise Ligue Canc,INSERM,U917, F-35000 Rennes, France$$aMourcin, Frederic
000223214 700__ $$uMem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA$$aSanghvi, Viraj
000223214 700__ $$uUniv Rennes 1, EFS Bretagne, CHU Rennes, Equipe Labellise Ligue Canc,INSERM,U917, F-35000 Rennes, France$$aAmin, Rada
000223214 700__ $$0248688$$g253104$$uEcole Polytech Fed Lausanne, Swiss Inst Canc Res ISREC, SV Batiment 19, CH-1003 Lausanne, Switzerland$$aOricchio, Elisa
000223214 700__ $$uMem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA$$aJiang, Man
000223214 700__ $$uBritish Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 1L3, Canada$$aMottok, Anja
000223214 700__ $$uUniv Limoges, UMR 7276, CNRS, F-8700 Limoges, France$$aDenis-Lagache, Nicolas
000223214 700__ $$uUniv Lausanne, Dept Computat Biol, Rue Bugnon 27, CH-1005 Lausanne, Switzerland$$aCiriello, Giovanni
000223214 700__ $$uWeill Cornell Med Sch, Dept Pathol & Lab Med, New York, NY 10065 USA$$aTam, Wayne
000223214 700__ $$uMt Sinai Hlth Syst, Dept Pathol, New York, NY 10029 USA$$aTeruya-Feldstein, Julie
000223214 700__ $$aDe Stanchina, Elisa
000223214 700__ $$uCity Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA$$aChan, Wing C.
000223214 700__ $$uUniv Michigan, Dept Internal Med, Div Hematol & Oncol, Ann Arbor, MI 48109 USA$$aMalek, Sami N.
000223214 700__ $$uBritish Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 1L3, Canada$$aEnnishi, Daisuke
000223214 700__ $$aBrentjens, Renier J.
000223214 700__ $$uBritish Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 1L3, Canada$$aGascoyne, Randy D.
000223214 700__ $$uUniv Limoges, UMR 7276, CNRS, F-8700 Limoges, France$$aCogne, Michel
000223214 700__ $$uUniv Rennes 1, EFS Bretagne, CHU Rennes, Equipe Labellise Ligue Canc,INSERM,U917, F-35000 Rennes, France$$aTarte, Karin
000223214 700__ $$aWendel, Hans-Guido$$uMem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10065 USA
000223214 773__ $$j167$$tCell$$k2$$q405-418.e13
000223214 909C0 $$xU12997$$0252514$$pUPORICCHIO
000223214 909CO $$pSV$$particle$$ooai:infoscience.tind.io:223214
000223214 917Z8 $$x148230
000223214 937__ $$aEPFL-ARTICLE-223214
000223214 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000223214 980__ $$aARTICLE