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Genetic deletion of HVEM in a leukemia B cell line promotes a preferential increase of PD-1(-) stem cell-like T cells over PD-1(+) T cells curbing tumor progression

INTRODUCTION: A high frequency of mutations affecting the gene encoding Herpes Virus Entry Mediator (HVEM, TNFRSF14) is a common clinical finding in a wide variety of human tumors, including those of hematological origin. METHODS: We have addressed how HVEM expression on A20 leukemia cells influence...

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Autores principales: del Rio, Maria-Luisa, de Juan, Carla Yago-Diez, Roncador, Giovanna, Caleiras, Eduardo, Álvarez-Esteban, Ramón, Pérez-Simón, José Antonio, Rodriguez-Barbosa, Jose-Ignacio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076739/
https://www.ncbi.nlm.nih.gov/pubmed/37033927
http://dx.doi.org/10.3389/fimmu.2023.1113858
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author del Rio, Maria-Luisa
de Juan, Carla Yago-Diez
Roncador, Giovanna
Caleiras, Eduardo
Álvarez-Esteban, Ramón
Pérez-Simón, José Antonio
Rodriguez-Barbosa, Jose-Ignacio
author_facet del Rio, Maria-Luisa
de Juan, Carla Yago-Diez
Roncador, Giovanna
Caleiras, Eduardo
Álvarez-Esteban, Ramón
Pérez-Simón, José Antonio
Rodriguez-Barbosa, Jose-Ignacio
author_sort del Rio, Maria-Luisa
collection PubMed
description INTRODUCTION: A high frequency of mutations affecting the gene encoding Herpes Virus Entry Mediator (HVEM, TNFRSF14) is a common clinical finding in a wide variety of human tumors, including those of hematological origin. METHODS: We have addressed how HVEM expression on A20 leukemia cells influences tumor survival and its involvement in the modulation of the anti-tumor immune responses in a parental into F1 mouse tumor model of hybrid resistance by knocking-out HVEM expression. HVEM WT or HVEM KO leukemia cells were then injected intravenously into semiallogeneic F1 recipients and the extent of tumor dissemination was evaluated. RESULTS: The loss of HVEM expression on A20 leukemia cells led to a significant increase of lymphoid and myeloid tumor cell infiltration curbing tumor progression. NK cells and to a lesser extent NKT cells and monocytes were the predominant innate populations contributing to the global increase of immune infiltrates in HVEM KO tumors compared to that present in HVEM KO tumors. In the overall increase of the adaptive T cell immune infiltrates, the stem cell-like PD-1(-) T cells progenitors and the effector T cell populations derived from them were more prominently present than terminally differentiated PD-1(+) T cells. CONCLUSIONS: These results suggest that the PD-1(-) T cell subpopulation is likely to be a more relevant contributor to tumor rejection than the PD-1(+) T cell subpopulation. These findings highlight the role of co-inhibitory signals delivered by HVEM upon engagement of BTLA on T cells and NK cells, placing HVEM/BTLA interaction in the spotlight as a novel immune checkpoint for the reinforcement of the anti-tumor responses in malignancies of hematopoietic origin.
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spelling pubmed-100767392023-04-07 Genetic deletion of HVEM in a leukemia B cell line promotes a preferential increase of PD-1(-) stem cell-like T cells over PD-1(+) T cells curbing tumor progression del Rio, Maria-Luisa de Juan, Carla Yago-Diez Roncador, Giovanna Caleiras, Eduardo Álvarez-Esteban, Ramón Pérez-Simón, José Antonio Rodriguez-Barbosa, Jose-Ignacio Front Immunol Immunology INTRODUCTION: A high frequency of mutations affecting the gene encoding Herpes Virus Entry Mediator (HVEM, TNFRSF14) is a common clinical finding in a wide variety of human tumors, including those of hematological origin. METHODS: We have addressed how HVEM expression on A20 leukemia cells influences tumor survival and its involvement in the modulation of the anti-tumor immune responses in a parental into F1 mouse tumor model of hybrid resistance by knocking-out HVEM expression. HVEM WT or HVEM KO leukemia cells were then injected intravenously into semiallogeneic F1 recipients and the extent of tumor dissemination was evaluated. RESULTS: The loss of HVEM expression on A20 leukemia cells led to a significant increase of lymphoid and myeloid tumor cell infiltration curbing tumor progression. NK cells and to a lesser extent NKT cells and monocytes were the predominant innate populations contributing to the global increase of immune infiltrates in HVEM KO tumors compared to that present in HVEM KO tumors. In the overall increase of the adaptive T cell immune infiltrates, the stem cell-like PD-1(-) T cells progenitors and the effector T cell populations derived from them were more prominently present than terminally differentiated PD-1(+) T cells. CONCLUSIONS: These results suggest that the PD-1(-) T cell subpopulation is likely to be a more relevant contributor to tumor rejection than the PD-1(+) T cell subpopulation. These findings highlight the role of co-inhibitory signals delivered by HVEM upon engagement of BTLA on T cells and NK cells, placing HVEM/BTLA interaction in the spotlight as a novel immune checkpoint for the reinforcement of the anti-tumor responses in malignancies of hematopoietic origin. Frontiers Media S.A. 2023-03-23 /pmc/articles/PMC10076739/ /pubmed/37033927 http://dx.doi.org/10.3389/fimmu.2023.1113858 Text en Copyright © 2023 del Rio, de Juan, Roncador, Caleiras, Álvarez-Esteban, Pérez-Simón and Rodriguez-Barbosa https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
del Rio, Maria-Luisa
de Juan, Carla Yago-Diez
Roncador, Giovanna
Caleiras, Eduardo
Álvarez-Esteban, Ramón
Pérez-Simón, José Antonio
Rodriguez-Barbosa, Jose-Ignacio
Genetic deletion of HVEM in a leukemia B cell line promotes a preferential increase of PD-1(-) stem cell-like T cells over PD-1(+) T cells curbing tumor progression
title Genetic deletion of HVEM in a leukemia B cell line promotes a preferential increase of PD-1(-) stem cell-like T cells over PD-1(+) T cells curbing tumor progression
title_full Genetic deletion of HVEM in a leukemia B cell line promotes a preferential increase of PD-1(-) stem cell-like T cells over PD-1(+) T cells curbing tumor progression
title_fullStr Genetic deletion of HVEM in a leukemia B cell line promotes a preferential increase of PD-1(-) stem cell-like T cells over PD-1(+) T cells curbing tumor progression
title_full_unstemmed Genetic deletion of HVEM in a leukemia B cell line promotes a preferential increase of PD-1(-) stem cell-like T cells over PD-1(+) T cells curbing tumor progression
title_short Genetic deletion of HVEM in a leukemia B cell line promotes a preferential increase of PD-1(-) stem cell-like T cells over PD-1(+) T cells curbing tumor progression
title_sort genetic deletion of hvem in a leukemia b cell line promotes a preferential increase of pd-1(-) stem cell-like t cells over pd-1(+) t cells curbing tumor progression
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076739/
https://www.ncbi.nlm.nih.gov/pubmed/37033927
http://dx.doi.org/10.3389/fimmu.2023.1113858
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