title: T-cell defect in diffuse large B-cell lymphomas involves expansion of myeloid-derived suppressor cells.
abstract: In diffuse large B-cell lymphoma (DLBCL), the number of circulating monocytes and neutrophils represents an independent prognostic factor. These cell subsets include monocytic and granulocytic myeloid-derived suppressor cells (M- and G-MDSCs) defined by their ability to suppress T-cell responses. MDSCs are a heterogeneous population described in inflammatory and infectious diseases and in numerous tumors including multiple myeloma, chronic lymphocytic leukemia, and DLBCL. However, their mechanisms of action remain unclear. We broadly assessed the presence and mechanisms of suppression of MDSC subsets in DLBCL. First, a myeloid suppressive signature was identified by gene expression profiling in DLBCL peripheral blood. Accordingly, we identified, in a cohort of 66 DLBCL patients, an increase in circulating G-MDSC (Lin(neg)HLA-DR(neg)CD33(pos)CD11b(pos)) and M-MDSC (CD14(pos)HLA-DR(low)) counts. Interestingly, only M-MDSC number was correlated with the International Prognostic Index, event-free survival, and number of circulating Tregs. Furthermore, T-cell proliferation was restored after monocyte depletion. Myeloid-dependent T-cell suppression was attributed to a release of interleukin-10 and S100A12 and increased PD-L1 expression. In summary, we identified expanded MDSC subsets in DLBCL, as well as new mechanisms of immunosuppression in DLBCL.
authors.affiliation: Pôle Biologie and.
authors.forename: Imane
authors.initials: I
authors.lastname: Azzaoui
authors.affiliation: Maladies Infectieuses et Réanimation Médicale, Centre Hospitalier Universitaire de Rennes, Rennes, France; INSERM, Unité Mixte de Recherche U917, Equipe Labellisée Ligue Contre le Cancer, Rennes, France; Université Rennes 1, Unité Mixte de Recherche U917, Rennes, France; Etablissement Français du Sang Bretagne, Rennes, France;
authors.forename: Fabrice
authors.initials: F
authors.lastname: Uhel
authors.affiliation: Pôle Biologie and INSERM, Unité Mixte de Recherche U917, Equipe Labellisée Ligue Contre le Cancer, Rennes, France; Université Rennes 1, Unité Mixte de Recherche U917, Rennes, France; Etablissement Français du Sang Bretagne, Rennes, France;
authors.forename: Delphine
authors.initials: D
authors.lastname: Rossille
authors.affiliation: Pôle Biologie and INSERM, Unité Mixte de Recherche U917, Equipe Labellisée Ligue Contre le Cancer, Rennes, France; Université Rennes 1, Unité Mixte de Recherche U917, Rennes, France; Etablissement Français du Sang Bretagne, Rennes, France;
authors.forename: Celine
authors.initials: C
authors.lastname: Pangault
authors.affiliation: Pôle Biologie and INSERM, Unité Mixte de Recherche U917, Equipe Labellisée Ligue Contre le Cancer, Rennes, France; Université Rennes 1, Unité Mixte de Recherche U917, Rennes, France; Etablissement Français du Sang Bretagne, Rennes, France;
authors.forename: Joelle
authors.initials: J
authors.lastname: Dulong
authors.affiliation: Pôle Biologie and.
authors.forename: Jerome
authors.initials: J
authors.lastname: Le Priol
authors.affiliation: INSERM, Unité Mixte de Recherche U917, Equipe Labellisée Ligue Contre le Cancer, Rennes, France; Université Rennes 1, Unité Mixte de Recherche U917, Rennes, France; Etablissement Français du Sang Bretagne, Rennes, France; Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Rennes, Rennes, France;
authors.forename: Thierry
authors.initials: T
authors.lastname: Lamy
authors.affiliation: INSERM, Unité Mixte de Recherche U917, Equipe Labellisée Ligue Contre le Cancer, Rennes, France; Université Rennes 1, Unité Mixte de Recherche U917, Rennes, France; Etablissement Français du Sang Bretagne, Rennes, France; Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Rennes, Rennes, France;
authors.forename: Roch
authors.initials: R
authors.lastname: Houot
authors.affiliation: Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Nantes, Unité Mixte de Recherche 892 équipe 10, Nantes, France;
authors.forename: Steven
authors.initials: S
authors.lastname: Le Gouill
authors.affiliation: Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Montpellier, Montpellier, France;
authors.forename: Guillaume
authors.initials: G
authors.lastname: Cartron
authors.affiliation: Unité d'Hématologie Clinique, Centre Hospitalier de Bretagne Atlantique, Vannes, France;
authors.forename: Pascal
authors.initials: P
authors.lastname: Godmer
authors.affiliation: Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France; and.
authors.forename: Krimo
authors.initials: K
authors.lastname: Bouabdallah
authors.affiliation: Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France; and.
authors.forename: Noel
authors.initials: N
authors.lastname: Milpied
authors.affiliation: Service d'Hématologie Clinique, Centre Hospitalier Universitaire de Caen, Caen, France.
authors.forename: Gandhi
authors.identifier: 0000-0001-6402-320X
authors.initials: G
authors.lastname: Damaj
authors.affiliation: Pôle Biologie and INSERM, Unité Mixte de Recherche U917, Equipe Labellisée Ligue Contre le Cancer, Rennes, France; Université Rennes 1, Unité Mixte de Recherche U917, Rennes, France; Etablissement Français du Sang Bretagne, Rennes, France;
authors.forename: Karin
authors.identifier: 0000-0002-6809-917X
authors.initials: K
authors.lastname: Tarte
authors.affiliation: Pôle Biologie and INSERM, Unité Mixte de Recherche U917, Equipe Labellisée Ligue Contre le Cancer, Rennes, France; Université Rennes 1, Unité Mixte de Recherche U917, Rennes, France; Etablissement Français du Sang Bretagne, Rennes, France;
authors.forename: Thierry
authors.initials: T
authors.lastname: Fest
authors.affiliation: Pôle Biologie and INSERM, Unité Mixte de Recherche U917, Equipe Labellisée Ligue Contre le Cancer, Rennes, France; Université Rennes 1, Unité Mixte de Recherche U917, Rennes, France; Etablissement Français du Sang Bretagne, Rennes, France;
authors.forename: Mikael
authors.identifier: 0000-0002-9741-0668
authors.initials: M
authors.lastname: Roussel
mesh_terms: D001119:Arginase / Q000378:metabolism; D060890:B7-H1 Antigen / Q000378:metabolism; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007165:Immunosuppression Therapy; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000276:immunology*; D009000:Monocytes / Q000378:metabolism; D000072737:Myeloid-Derived Suppressor Cells / Q000378:metabolism / Q000473:pathology*; D000067616:S100A12 Protein / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D000067616:S100A12 Protein; C090441:S100A12 protein, human; D016753:Interleukin-10; D001119:Arginase