Innate T-αβ lymphocytes as new immunological components of anti-tumoral “off-target” effects of the tyrosine kinase inhibitor dasatinib

Abstract 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...

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Autores principales:	Alice Barbarin, Myriam Abdallah, Lucie Lefèvre, Nathalie Piccirilli, Emilie Cayssials, Lydia Roy, Jean-Marc Gombert, André Herbelin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/93d95eabd8174e51acc184d4b1943df3
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spelling	oai:doaj.org-article:93d95eabd8174e51acc184d4b1943df32021-12-02T11:02:23ZInnate T-αβ lymphocytes as new immunological components of anti-tumoral “off-target” effects of the tyrosine kinase inhibitor dasatinib10.1038/s41598-020-60195-z2045-2322https://doaj.org/article/93d95eabd8174e51acc184d4b1943df32020-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-60195-zhttps://doaj.org/toc/2045-2322Abstract 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-αβ 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 IFNγ 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-αβ cells, thereby opening new opportunities for chemoimmunotherapy.Alice BarbarinMyriam AbdallahLucie LefèvreNathalie PiccirilliEmilie CayssialsLydia RoyJean-Marc GombertAndré HerbelinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-9 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alice Barbarin Myriam Abdallah Lucie Lefèvre Nathalie Piccirilli Emilie Cayssials Lydia Roy Jean-Marc Gombert André Herbelin Innate T-αβ lymphocytes as new immunological components of anti-tumoral “off-target” effects of the tyrosine kinase inhibitor dasatinib
description	Abstract 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-αβ 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 IFNγ 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-αβ cells, thereby opening new opportunities for chemoimmunotherapy.
format	article
author	Alice Barbarin Myriam Abdallah Lucie Lefèvre Nathalie Piccirilli Emilie Cayssials Lydia Roy Jean-Marc Gombert André Herbelin
author_facet	Alice Barbarin Myriam Abdallah Lucie Lefèvre Nathalie Piccirilli Emilie Cayssials Lydia Roy Jean-Marc Gombert André Herbelin
author_sort	Alice Barbarin
title	Innate T-αβ lymphocytes as new immunological components of anti-tumoral “off-target” effects of the tyrosine kinase inhibitor dasatinib
title_short	Innate T-αβ lymphocytes as new immunological components of anti-tumoral “off-target” effects of the tyrosine kinase inhibitor dasatinib
title_full	Innate T-αβ lymphocytes as new immunological components of anti-tumoral “off-target” effects of the tyrosine kinase inhibitor dasatinib
title_fullStr	Innate T-αβ lymphocytes as new immunological components of anti-tumoral “off-target” effects of the tyrosine kinase inhibitor dasatinib
title_full_unstemmed	Innate T-αβ lymphocytes as new immunological components of anti-tumoral “off-target” effects of the tyrosine kinase inhibitor dasatinib
title_sort	innate t-αβ lymphocytes as new immunological components of anti-tumoral “off-target” effects of the tyrosine kinase inhibitor dasatinib
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/93d95eabd8174e51acc184d4b1943df3
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Innate T-αβ lymphocytes as new immunological components of anti-tumoral “off-target” effects of the tyrosine kinase inhibitor dasatinib

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