期刊
SCIENTIFIC REPORTS
卷 10, 期 1, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-020-60195-z
关键词
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资金
- INSERM
- CHU de Poitiers
- Universite de Poitiers
- Ligue contre le Cancer du Grand Ouest (Comites departementaux de la Vienne, de la Charente, de la Charente Maritime et des Deux-Sevres)
- Association pour la Recherche en Immunologie-Poitou-Charentes (ARIM-PC)
- Canceropole Grand Sud-Ouest
- Groupement Interregional de Recherche Clinique et d'Innovation Sud-Ouest Outre-Mer (API-K 2017)
- Association Laurette Fugain [ALF 2015/10, ALF 2019/10]
- Fondation Brystol-Meyers Squibb
- Region Nouvelle Aquitaine
- Sport & Collection fellowship
- [INCa-DGOS 8658 (PRT-K 2015-052)]
Kinase inhibitors hold great potential as targeted therapy against malignant cells. Among them, the tyrosine kinase inhibitor dasatinib is known for a number of clinically relevant off-target actions, attributed in part to effects on components of the immune system, especially conventional T-cells and natural killer (NK)-cells. Here, we have hypothesized that dasatinib also influences non-conventional T-alpha beta cell subsets known for their potential anti-tumoral properties, namely iNKT cells and the distinct new innate CD8 T-cell subset. In mice, where the two subsets were originally characterized, an activated state of iNKT cells associated with a shift toward an iNKT cell Th1-phenotype was observed after dasatinib treatment in vivo. Despite decreased frequency of the total memory CD8 T-cell compartment, the proportion of innate-memory CD8 T-cells and their IFN gamma expression in response to an innate-like stimulation increased in response to dasatinib. Lastly, in patients administered with dasatinib for the treatment of BCR-ABL-positive leukemias, we provided the proof of concept that the kinase inhibitor also influences the two innate T-cell subsets in humans, as attested by their increased frequency in the peripheral blood. These data highlight the potential immunostimulatory capacity of dasatinib on innate T-alpha beta cells, thereby opening new opportunities for chemoimmunotherapy.
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