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

• DOI: 10.1186/s12964-019-0391-x
• Publication Date: 2019-08-05T13:03:03Z
• Authors: Christelle Vincen...; Lilian Roland; Ursula Zimber-Strobl; Jean Feuillard; Nathalie Faumont
• Keywords: breakpoint cluster region

Escape from immune control must be important in the natural course of B-cell lymphomas, especially for those with activation NF-κB. The pre-clinical LMP1/CD40-expressing transgenic mouse model is characterized by specific CD40 signaling responsible NF-κB continuous a spleen monoclonal tumor after 1 year 60% cases. LMP1/CD40 tumors B-cells expressed high levels PD-L1. This expression was dependent on either NF-κB, JAK1/JAK2 or BTK pathways since these were activated and ex vivo treatment inhibitory molecules PHA-408, ruxolitinib ibrutinib led to decrease its expression. Treatment lymphomatous mice an anti-PD-L1 antibody induced regression decreased content, proliferation rate as well marked increase T-cell activation, assessed CD62L CD44 These results highlight interest therapies targeting PD-1/PD-L1 axis lymphomas PD-L1 expression, possible synergies tyrosine kinase inhibitors.