PuSH - Publikationsserver des Helmholtz Zentrums München

Vincent-Fabert, C.* ; Roland, L.* ; Zimber-Strobl, U. ; Feuillard, J.* ; Faumont, N.*

Pre-clinical blocking of PD-L1 molecule, which expression is down regulated by NF-κB, JAK1/JAK2 and BTK inhibitors, induces regression of activated B-cell lymphoma.

κκκ

Cell Commun. Signal. 17:89 (2019)
Verlagsversion DOI
Open Access Gold
Creative Commons Lizenzvertrag
Escape from immune control must be important in the natural course of B-cell lymphomas, especially for those with activation of NF-kappa B. The pre-clinical LMP1/CD40-expressing transgenic mouse model is characterized by B-cell specific CD40 signaling responsible for NF-kappa B continuous activation with a spleen monoclonal B-cell tumor after 1 year in 60% of cases. LMP1/CD40 tumors B-cells expressed high levels of PD-L1. This expression was dependent on activation of either NF-kappa B, JAK1/JAK2 or BTK pathways since these pathways were activated in tumor B-cells and ex vivo treatment with the inhibitory molecules PHA-408, ruxolitinib and ibrutinib led to decrease of its expression. Treatment of LMP1/CD40-expressing lymphomatous mice with an anti-PD-L1 monoclonal antibody induced tumor regression with decreased spleen content, activation and proliferation rate of B-cells as well as a marked increase in T-cell activation, as assessed by CD62L and CD44 expression. These results highlight the interest of therapies targeting the PD-1/PD-L1 axis in activated lymphomas with PD-L1 expression, with possible synergies with tyrosine kinase inhibitors.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter B-cell Lymphomas ; Pd-l1 ; Immune Surveillance; Signaling Pathway; C-myc; Receptor; Blockade
ISSN (print) / ISBN 1478-811X
e-ISSN 1478-811X
Zeitschrift Cell Communication and Signaling
Quellenangaben Band: 17, Heft: 1, Seiten: , Artikelnummer: 89 Supplement: ,
Verlag BioMed Central
Verlagsort Campus, 4 Crinan St, London N1 9xw, England
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Gene Vector (AGV)