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Characterization of the DNAM-1, TIGIT and TACTILE Axis on Circulating NK, NKT-Like and T Cell Subsets in Patients with Acute Myeloid Leukemia

Background: Acute myeloid leukemia (AML) remains a major clinical challenge due to poor overall survival, which is even more dramatic in elderly patients. TIGIT, an inhibitory receptor that interacts with CD155 and CD112 molecules, is considered as a checkpoint in T and NK cell activation. This rece...

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Autores principales: Valhondo, Isabel, Hassouneh, Fakhri, Lopez-Sejas, Nelson, Pera, Alejandra, Sanchez-Correa, Beatriz, Guerrero, Beatriz, Bergua, Juan M., Arcos, Maria Jose, Bañas, Helena, Casas-Avilés, Ignacio, Sanchez-Garcia, Joaquin, Serrano, Josefina, Martin, Carmen, Duran, Esther, Alonso, Corona, Solana, Rafael, Tarazona, Raquel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464787/
https://www.ncbi.nlm.nih.gov/pubmed/32764229
http://dx.doi.org/10.3390/cancers12082171
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author Valhondo, Isabel
Hassouneh, Fakhri
Lopez-Sejas, Nelson
Pera, Alejandra
Sanchez-Correa, Beatriz
Guerrero, Beatriz
Bergua, Juan M.
Arcos, Maria Jose
Bañas, Helena
Casas-Avilés, Ignacio
Sanchez-Garcia, Joaquin
Serrano, Josefina
Martin, Carmen
Duran, Esther
Alonso, Corona
Solana, Rafael
Tarazona, Raquel
author_facet Valhondo, Isabel
Hassouneh, Fakhri
Lopez-Sejas, Nelson
Pera, Alejandra
Sanchez-Correa, Beatriz
Guerrero, Beatriz
Bergua, Juan M.
Arcos, Maria Jose
Bañas, Helena
Casas-Avilés, Ignacio
Sanchez-Garcia, Joaquin
Serrano, Josefina
Martin, Carmen
Duran, Esther
Alonso, Corona
Solana, Rafael
Tarazona, Raquel
author_sort Valhondo, Isabel
collection PubMed
description Background: Acute myeloid leukemia (AML) remains a major clinical challenge due to poor overall survival, which is even more dramatic in elderly patients. TIGIT, an inhibitory receptor that interacts with CD155 and CD112 molecules, is considered as a checkpoint in T and NK cell activation. This receptor shares ligands with the co-stimulatory receptor DNAM-1 and with TACTILE. The aim of this work was to analyze the expression of DNAM-1, TIGIT and TACTILE in NK cells and T cell subsets in AML patients. Methods: We have studied 36 patients at the time of diagnosis of AML and 20 healthy volunteers. The expression of DNAM-1, TIGIT and TACTILE in NK cells and T cells, according to the expression of CD3 and CD56, was performed by flow cytometry. Results: NK cells, CD56− T cells and CD56+ T (NKT-like) cells from AML patients presented a reduced expression of DNAM-1 compared with healthy volunteers. An increased expression of TIGIT was observed in mainstream CD56− T cells. No differences were observed in the expression of TACTILE. Simplified presentation of incredibly complex evaluations (SPICE) analysis of the co-expression of DNAM-1, TIGIT and TACTILE showed an increase in NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE. Low percentages of DNAM-1−TIGIT+TACTILE+ NK cells and DNAM-1− TIGIT+TACTILE+ CD56− T cells were associated with a better survival of AML patients. Conclusions: The expression of DNAM-1 is reduced in NK cells and in CD4+ and CD8+ T cells from AML patients compared with those from healthy volunteers. An increased percentage of NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE is associated with patient survival, supporting the role of TIGIT as a novel candidate for checkpoint blockade.
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spelling pubmed-74647872020-09-04 Characterization of the DNAM-1, TIGIT and TACTILE Axis on Circulating NK, NKT-Like and T Cell Subsets in Patients with Acute Myeloid Leukemia Valhondo, Isabel Hassouneh, Fakhri Lopez-Sejas, Nelson Pera, Alejandra Sanchez-Correa, Beatriz Guerrero, Beatriz Bergua, Juan M. Arcos, Maria Jose Bañas, Helena Casas-Avilés, Ignacio Sanchez-Garcia, Joaquin Serrano, Josefina Martin, Carmen Duran, Esther Alonso, Corona Solana, Rafael Tarazona, Raquel Cancers (Basel) Article Background: Acute myeloid leukemia (AML) remains a major clinical challenge due to poor overall survival, which is even more dramatic in elderly patients. TIGIT, an inhibitory receptor that interacts with CD155 and CD112 molecules, is considered as a checkpoint in T and NK cell activation. This receptor shares ligands with the co-stimulatory receptor DNAM-1 and with TACTILE. The aim of this work was to analyze the expression of DNAM-1, TIGIT and TACTILE in NK cells and T cell subsets in AML patients. Methods: We have studied 36 patients at the time of diagnosis of AML and 20 healthy volunteers. The expression of DNAM-1, TIGIT and TACTILE in NK cells and T cells, according to the expression of CD3 and CD56, was performed by flow cytometry. Results: NK cells, CD56− T cells and CD56+ T (NKT-like) cells from AML patients presented a reduced expression of DNAM-1 compared with healthy volunteers. An increased expression of TIGIT was observed in mainstream CD56− T cells. No differences were observed in the expression of TACTILE. Simplified presentation of incredibly complex evaluations (SPICE) analysis of the co-expression of DNAM-1, TIGIT and TACTILE showed an increase in NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE. Low percentages of DNAM-1−TIGIT+TACTILE+ NK cells and DNAM-1− TIGIT+TACTILE+ CD56− T cells were associated with a better survival of AML patients. Conclusions: The expression of DNAM-1 is reduced in NK cells and in CD4+ and CD8+ T cells from AML patients compared with those from healthy volunteers. An increased percentage of NK and T cells lacking DNAM-1 and co-expressing TIGIT and TACTILE is associated with patient survival, supporting the role of TIGIT as a novel candidate for checkpoint blockade. MDPI 2020-08-05 /pmc/articles/PMC7464787/ /pubmed/32764229 http://dx.doi.org/10.3390/cancers12082171 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Valhondo, Isabel
Hassouneh, Fakhri
Lopez-Sejas, Nelson
Pera, Alejandra
Sanchez-Correa, Beatriz
Guerrero, Beatriz
Bergua, Juan M.
Arcos, Maria Jose
Bañas, Helena
Casas-Avilés, Ignacio
Sanchez-Garcia, Joaquin
Serrano, Josefina
Martin, Carmen
Duran, Esther
Alonso, Corona
Solana, Rafael
Tarazona, Raquel
Characterization of the DNAM-1, TIGIT and TACTILE Axis on Circulating NK, NKT-Like and T Cell Subsets in Patients with Acute Myeloid Leukemia
title Characterization of the DNAM-1, TIGIT and TACTILE Axis on Circulating NK, NKT-Like and T Cell Subsets in Patients with Acute Myeloid Leukemia
title_full Characterization of the DNAM-1, TIGIT and TACTILE Axis on Circulating NK, NKT-Like and T Cell Subsets in Patients with Acute Myeloid Leukemia
title_fullStr Characterization of the DNAM-1, TIGIT and TACTILE Axis on Circulating NK, NKT-Like and T Cell Subsets in Patients with Acute Myeloid Leukemia
title_full_unstemmed Characterization of the DNAM-1, TIGIT and TACTILE Axis on Circulating NK, NKT-Like and T Cell Subsets in Patients with Acute Myeloid Leukemia
title_short Characterization of the DNAM-1, TIGIT and TACTILE Axis on Circulating NK, NKT-Like and T Cell Subsets in Patients with Acute Myeloid Leukemia
title_sort characterization of the dnam-1, tigit and tactile axis on circulating nk, nkt-like and t cell subsets in patients with acute myeloid leukemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464787/
https://www.ncbi.nlm.nih.gov/pubmed/32764229
http://dx.doi.org/10.3390/cancers12082171
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