CORRELATION BETWEEN PRE-TREATMENT LEVEL OF SOLUBLE PD-L1 AND OUTCOME IN CLASSICAL HODGKIN LYMPHOMA INCLUDED IN A PROSPECTIVE STUDY OF THE LYMPHOMA STUDY ASSOCIATION

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CD40L-expressing CD4+ T cells prime adipose-derived stromal cells to produce inflammatory chemokines

International audienceThe therapeutic potential of culture-adapted adipose-derived stromal cells (ASCs) is largely related to their production of immunosuppressive factors that are inducible in vitro by priming with inflammatory stimuli, in particular tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ). In vivo, obesity is associated with chronic inflammation of white adipose tissue, including accumulation of neutrophils, infiltration by IFNγ/TNFα-producing immune cells, and ASC dysfunction. In the current study, we identified in obese patients a simultaneous upregulation of CD40Lin the adipose tissue stroma vascular fraction (AT-SVF), correlated with the Th1 gene signature, and an overexpression of CD40 by native ASCs. Moreover, activated CD4+ T cells upregulated CD40 on culture-expanded ASCs and triggered their production of IL-8 in a CD40L-dependent manner, leading to an increased capacity to recruit neutrophils. Finally, activation of ASCs by sCD40L or CD40L-expressing CD4+ T cells relies on both canonical and non-canonical NF-κB pathways, and IL-8 was found to be coregulated with NF-κB family members in AT-SVF. These data identify the CD40-CD40L axis as a priming mechanism of ASCs, able to modulate their cross talk with neutrophils in an inflammatory context, and their functional capacity for therapeutic applications

High level of soluble programmed cell death ligand 1 in blood impacts overall survival in aggressive diffuse large B-Cell lymphoma: results from a french multicenter clinical trial.

International audienceThe dosage of soluble programmed cell death ligand 1 (sPD-L1) protein in the blood of adults with cancer has never been performed in a prospective patient cohort. We evaluated the clinical impact of sPD-L1 level measured at the time of diagnosis for newly diagnosed DLBCL. Soluble PD-L1 was measured in the plasma of 288 patients enrolled in a multicenter, randomized phase III trial that compared R-high-dose chemotherapy to R-CHOP. The median follow-up was 41.4 months. A cut-off of 1.52 ng/ml of PD-L1 level was determined and related to overall survival (OS). Patients with elevated sPD-L1 experienced a poorer prognosis with a three-year OS of 76% versus 89% (P<0.001). Considering clinical characteristics, the multivariate analysis retained this biomarker besides bone marrow involvement and abnormal lymphocyte-monocyte score as independently related to poor outcome. sPD-L1 was detectable in the plasma and not in the serum, found elevated in patients at diagnosis compared to healthy subjects and its level dropped back to normal value after CR. The intention-to-treat analysis showed that elevated sPD-L1 was associated with a poorer prognosis for patients randomized within the R-CHOP arm (P<0.001). Plasma PD-L1 protein is a potent predicting biomarker in DLBCL and may indicate usefulness of alternative therapeutic strategies using PD1 axis inhibitors