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.
journal_name
Bloodjournal_title
Bloodauthors
Azzaoui I,Uhel F,Rossille D,Pangault C,Dulong J,Le Priol J,Lamy T,Houot R,Le Gouill S,Cartron G,Godmer P,Bouabdallah K,Milpied N,Damaj G,Tarte K,Fest T,Roussel Mdoi
10.1182/blood-2015-08-662783subject
Has Abstractpub_date
2016-08-25 00:00:00pages
1081-92issue
8eissn
0006-4971issn
1528-0020pii
blood-2015-08-662783journal_volume
128pub_type
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