T-cell defect in Diffuse Large B-cell Lymphomas involves expansion of myeloid derived suppressor cells expressing IL-10, PD-L1 and S100A12

Imane Azzaoui (1, 2) , Fabrice Uhel (3, 1, 2) , Delphine Rossille (3, 1, 2) , Celine Pangault (3, 1, 2) , Joelle Dulong (3, 1, 2) , Jerome Le Priol (3, 1, 2) , Thierry Lamy (3, 1, 2) , Roch Houot (3, 1, 2) , Steven Le Gouill (4) , Guillaume Cartron (5) , Pascal Godmer (6) , Krimo Bouabdallah (7) , Noel Milpied (7) , Gandhi Damaj (8) , Karin Tarte (3, 1, 2) , Thierry Fest (3, 1, 2) , Mikael Roussel (2, 3, 1)

1 CHU Pontchaillou [Rennes]
2 EFS Bretagne - Etablissement français du sang [Rennes]
3 MiCa - Microenvironnement et cancer
4 CHU Nantes - Centre hospitalier universitaire de Nantes
5 Hôpital Gui de Chauliac
6 CHBA - Centre hospitalier Bretagne Atlantique (Morbihan)
7 CHU Bordeaux [Bordeaux]
8 CHU Caen

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 (LinnegHLA-DRnegCD33posCD11bpos) and M-MDSC (CD14posHLA-DRlow) 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.

Domains: Life Sciences [q-bio]; Cancer

Imane Azzaoui, Fabrice Uhel, Delphine Rossille, Celine Pangault, Joelle Dulong, et al.. T-cell defect in Diffuse Large B-cell Lymphomas involves expansion of myeloid derived suppressor cells expressing IL-10, PD-L1 and S100A12. Blood, 2016, 128 (8), pp.1081-1092. ⟨10.1182/blood-2015-08-662783⟩. ⟨hal-01394657⟩