期刊
CELL COMMUNICATION AND SIGNALING
卷 17, 期 1, 页码 -出版社
BMC
DOI: 10.1186/s12964-019-0391-x
关键词
B-cell lymphomas; PD-L1; Immune surveillance
类别
资金
- Ligue National contre le Cancer (Equipe Labellisee Ligue)
- Institut National du Cancer (INCa)
- Comite Orientation Recherche Cancer (CORC)
- Limousin Region
- Haute Vienne committee of Ligue Nationale Contre le Cancer
- German Research Foundation [SFB 1243, TP-A13]
- Lyons Club of Correze
- Correze committee of Ligue Nationale Contre le Cancer
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.
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