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.

journal_name

Blood

journal_title

Blood

authors

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 M

doi

10.1182/blood-2015-08-662783

subject

Has Abstract

pub_date

2016-08-25 00:00:00

pages

1081-92

issue

8

eissn

0006-4971

issn

1528-0020

pii

blood-2015-08-662783

journal_volume

128

pub_type

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