Activated naïve γδ T cells accelerate deep molecular response to BCR-ABL inhibitors in patients with chronic myeloid leukemia

Abstract Tyrosine kinase inhibitors (TKIs) that target BCR-ABL are the frontline treatments in chronic myeloid leukemia (CML). Growing evidence has shown that TKIs also enhance immunity. Since gamma-delta T (γδT) cells possess the potent anticancer capability, here we investigated the potential invo...

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Autores principales:	Yu-Cheng Chang, Yi-Hao Chiang, Kate Hsu, Chih-Kuang Chuang, Chen-Wei Kao, Yi-Fang Chang, Ming-Chih Chang, Ken-Hong Lim, Hung-I Cheng, Yen-Ning Hsu, Caleb G. Chen
Formato:	article
Lenguaje:	EN
Publicado:	Nature Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/9de7eaa081b649b584d078d1f35041b7
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spelling	oai:doaj.org-article:9de7eaa081b649b584d078d1f35041b72021-11-21T12:42:14ZActivated naïve γδ T cells accelerate deep molecular response to BCR-ABL inhibitors in patients with chronic myeloid leukemia10.1038/s41408-021-00572-72044-5385https://doaj.org/article/9de7eaa081b649b584d078d1f35041b72021-11-01T00:00:00Zhttps://doi.org/10.1038/s41408-021-00572-7https://doaj.org/toc/2044-5385Abstract Tyrosine kinase inhibitors (TKIs) that target BCR-ABL are the frontline treatments in chronic myeloid leukemia (CML). Growing evidence has shown that TKIs also enhance immunity. Since gamma-delta T (γδT) cells possess the potent anticancer capability, here we investigated the potential involvement of γδT cells in TKI treatments for CML. We characterized γδT cells isolated from chronic-phase CML patients before and during TKI treatments. γδT expression increased significantly in CML patients who achieved major molecular response (MMR) and deep molecular response (DMR). Their Vδ2 subset of γδT also expanded, and increased expression of activating molecules, namely IFN-γ, perforin, and CD107a, as well as γδT cytotoxicity. Mechanistically, TKIs augmented the efflux of isopentenyl pyrophosphate (IPP) from CML cells, which stimulated IFN-γ production and γδT expansion. Notably, the size of the IFN-γ+ naïve γδT population in TKI-treated CML patients was strongly correlated with their rates to reach DMR and with the duration on DMR. Statistical analysis suggests that a cutoff of 7.5% IFN-γ+ naïve subpopulation of γδT in CML patients could serve as a determinant for MR4.0 sustainability. Our results highlight γδT cells as a positive regulator for TKI responses in CML patients.Yu-Cheng ChangYi-Hao ChiangKate HsuChih-Kuang ChuangChen-Wei KaoYi-Fang ChangMing-Chih ChangKen-Hong LimHung-I ChengYen-Ning HsuCaleb G. ChenNature Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENBlood Cancer Journal, Vol 11, Iss 11, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Yu-Cheng Chang Yi-Hao Chiang Kate Hsu Chih-Kuang Chuang Chen-Wei Kao Yi-Fang Chang Ming-Chih Chang Ken-Hong Lim Hung-I Cheng Yen-Ning Hsu Caleb G. Chen Activated naïve γδ T cells accelerate deep molecular response to BCR-ABL inhibitors in patients with chronic myeloid leukemia
description	Abstract Tyrosine kinase inhibitors (TKIs) that target BCR-ABL are the frontline treatments in chronic myeloid leukemia (CML). Growing evidence has shown that TKIs also enhance immunity. Since gamma-delta T (γδT) cells possess the potent anticancer capability, here we investigated the potential involvement of γδT cells in TKI treatments for CML. We characterized γδT cells isolated from chronic-phase CML patients before and during TKI treatments. γδT expression increased significantly in CML patients who achieved major molecular response (MMR) and deep molecular response (DMR). Their Vδ2 subset of γδT also expanded, and increased expression of activating molecules, namely IFN-γ, perforin, and CD107a, as well as γδT cytotoxicity. Mechanistically, TKIs augmented the efflux of isopentenyl pyrophosphate (IPP) from CML cells, which stimulated IFN-γ production and γδT expansion. Notably, the size of the IFN-γ+ naïve γδT population in TKI-treated CML patients was strongly correlated with their rates to reach DMR and with the duration on DMR. Statistical analysis suggests that a cutoff of 7.5% IFN-γ+ naïve subpopulation of γδT in CML patients could serve as a determinant for MR4.0 sustainability. Our results highlight γδT cells as a positive regulator for TKI responses in CML patients.
format	article
author	Yu-Cheng Chang Yi-Hao Chiang Kate Hsu Chih-Kuang Chuang Chen-Wei Kao Yi-Fang Chang Ming-Chih Chang Ken-Hong Lim Hung-I Cheng Yen-Ning Hsu Caleb G. Chen
author_facet	Yu-Cheng Chang Yi-Hao Chiang Kate Hsu Chih-Kuang Chuang Chen-Wei Kao Yi-Fang Chang Ming-Chih Chang Ken-Hong Lim Hung-I Cheng Yen-Ning Hsu Caleb G. Chen
author_sort	Yu-Cheng Chang
title	Activated naïve γδ T cells accelerate deep molecular response to BCR-ABL inhibitors in patients with chronic myeloid leukemia
title_short	Activated naïve γδ T cells accelerate deep molecular response to BCR-ABL inhibitors in patients with chronic myeloid leukemia
title_full	Activated naïve γδ T cells accelerate deep molecular response to BCR-ABL inhibitors in patients with chronic myeloid leukemia
title_fullStr	Activated naïve γδ T cells accelerate deep molecular response to BCR-ABL inhibitors in patients with chronic myeloid leukemia
title_full_unstemmed	Activated naïve γδ T cells accelerate deep molecular response to BCR-ABL inhibitors in patients with chronic myeloid leukemia
title_sort	activated naïve γδ t cells accelerate deep molecular response to bcr-abl inhibitors in patients with chronic myeloid leukemia
publisher	Nature Publishing Group
publishDate	2021
url	https://doaj.org/article/9de7eaa081b649b584d078d1f35041b7
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Activated naïve γδ T cells accelerate deep molecular response to BCR-ABL inhibitors in patients with chronic myeloid leukemia

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