Danielle Troutaud1, Hafidha Bentayeb2, Marine Aitamer3, Hussein Akil3, Chantal Vignoles3, Maud Branchaud2, Julie Abraham3,4, Nathalie Gachard3,5, Jean Feuillard3,5, Marie-Odile Jauberteau2, Hamasseh Shirvani6. 1. UMR CNRS 7276/INSERM U1262, Faculté de Médecine, Université de Limoges, 2 rue du Docteur Marcland, 87025, Limoges, Cedex, France. danielle.troutaud@unilim.fr. 2. EA3842 CAPTuR Facultés de Médecine et de Pharmacie, Université de Limoges, 2 rue du Docteur Marcland, 87025, Limoges, Cedex, France. 3. UMR CNRS 7276/INSERM U1262, Faculté de Médecine, Université de Limoges, 2 rue du Docteur Marcland, 87025, Limoges, Cedex, France. 4. Service d'Hématologie Clinique, CHU de Limoges, 2 Avenue Martin Luther King, 87000, Limoges, France. 5. Laboratoire d'hématologie, CHU de Limoges, 2 Avenue Martin Luther King, 87000, Limoges, France. 6. Institut Roche, 30, cours de l'île Seguin, 92650, Boulogne-Billancourt, France.
Abstract
BACKGROUND: Small extracellular vesicles (sEVs) including exosomes, carrying the CD20, could be involved in immunotherapy resistance in diffuse large B cell lymphoma (DLBCL). We have reported endogenous brain-derived neurotrophic factor/TrkB (tropomyosin-related kinase B) survival axis in DLBCL. Here, we performed a comparative study of sEV production by germinal centre B cell (GCB) and activated B cell (ABC)-DLBCL cell lines, and analysed TrkB activation on this process. METHODS: GCB (SUDHL4 and SUDHL6) and ABC (OCI-LY3, OCI-LY10 and U2932) cell lines were used. sEVs were characterised using nanoparticle tracking analysis technology and western blot. CD20 content was also analysed by enzyme-linked immunoassay, and complement-dependent cytotoxicity of rituximab was investigated. 7,8-Dihydroxyflavone (7,8-DHF) was used as a TrkB agonist. In vivo role of sEVs was evaluated in a xenograft model. RESULTS: sEVs production varied significantly between DLBCL cells, independently of subtype. CD20 level was consistent with that of parental cells. Higher CD20 expression was found in sEVs after TrkB activation, with a trend in increasing their concentration. sEVs determined in vitro and in vivo protection from rituximab, which seemed CD20 level-dependent; the protection was enhanced when sEVs were produced by 7,8-DHF-treated cells. CONCLUSIONS: DLBCL-derived sEVs have the differential capacity to interfere with immunotherapy, which could be enhanced by growth factors like neurotrophins. Evaluating the sEV CD20 level could be useful for disease monitoring.
BACKGROUND: Small extracellular vesicles (sEVs) including exosomes, carrying the CD20, could be involved in immunotherapy resistance in diffuse large B cell lymphoma (DLBCL). We have reported endogenous brain-derived neurotrophic factor/TrkB (tropomyosin-related kinase B) survival axis in DLBCL. Here, we performed a comparative study of sEV production by germinal centre B cell (GCB) and activated B cell (ABC)-DLBCL cell lines, and analysed TrkB activation on this process. METHODS: GCB (SUDHL4 and SUDHL6) and ABC (OCI-LY3, OCI-LY10 and U2932) cell lines were used. sEVs were characterised using nanoparticle tracking analysis technology and western blot. CD20 content was also analysed by enzyme-linked immunoassay, and complement-dependent cytotoxicity of rituximab was investigated. 7,8-Dihydroxyflavone (7,8-DHF) was used as a TrkB agonist. In vivo role of sEVs was evaluated in a xenograft model. RESULTS: sEVs production varied significantly between DLBCL cells, independently of subtype. CD20 level was consistent with that of parental cells. Higher CD20 expression was found in sEVs after TrkB activation, with a trend in increasing their concentration. sEVs determined in vitro and in vivo protection from rituximab, which seemed CD20 level-dependent; the protection was enhanced when sEVs were produced by 7,8-DHF-treated cells. CONCLUSIONS: DLBCL-derived sEVs have the differential capacity to interfere with immunotherapy, which could be enhanced by growth factors like neurotrophins. Evaluating the sEV CD20 level could be useful for disease monitoring.
Authors: George Wright; Bruce Tan; Andreas Rosenwald; Elaine H Hurt; Adrian Wiestner; Louis M Staudt Journal: Proc Natl Acad Sci U S A Date: 2003-08-04 Impact factor: 11.205
Authors: A A Alizadeh; M B Eisen; R E Davis; C Ma; I S Lossos; A Rosenwald; J C Boldrick; H Sabet; T Tran; X Yu; J I Powell; L Yang; G E Marti; T Moore; J Hudson; L Lu; D B Lewis; R Tibshirani; G Sherlock; W C Chan; T C Greiner; D D Weisenburger; J O Armitage; R Warnke; R Levy; W Wilson; M R Grever; J C Byrd; D Botstein; P O Brown; L M Staudt Journal: Nature Date: 2000-02-03 Impact factor: 49.962