ICAM-1-LFA-1 dependent CD8+ T-Lymphocyte aggregation in tumor tissue prevents recirculation to draining lymph nodes

The quantity of T-lymphocytes reaching the draining lymph nodes from tumors is likely important to mount effective distant responses and for the establishment of long term systemic memory. Looking into mechanisms behind lymphocyte egress, we directed our attention to leukocyte adhesion mechanisms in...

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Autores: Yanguas, A. (Alba)|||/items/7fd085ff-f8b5-4d04-beb0-44d2c5a45f19, Garasa, S. (Saray)|||/items/51924af8-57aa-477c-b3d8-886422be3713, Teijeira-Sánchez, A. (Álvaro)|||/items/8a954ec4-8458-46ea-b8e6-3165119bef30, Auba, C. (Cristina)|||/items/e35d9621-fca6-477a-b9f2-198573b0e8da, Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4e, Rouzaut, A. (Ana)|||/items/4cb4f93a-048e-4093-a125-f987ff4b9024
Tipo de recurso: artículo
Fecha de publicación:2018
País:España
Institución:Universidad de Navarra
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/56647
Acceso en línea:https://hdl.handle.net/10171/56647
Access Level:acceso abierto
Palabra clave:Draining lymph nodes
T-lymphocyte
Homotypic cell-adhesion
ICAM-1
Immune response
Cancer immunotherapy
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spelling ICAM-1-LFA-1 dependent CD8+ T-Lymphocyte aggregation in tumor tissue prevents recirculation to draining lymph nodesYanguas, A. (Alba)|||/items/7fd085ff-f8b5-4d04-beb0-44d2c5a45f19Garasa, S. (Saray)|||/items/51924af8-57aa-477c-b3d8-886422be3713Teijeira-Sánchez, A. (Álvaro)|||/items/8a954ec4-8458-46ea-b8e6-3165119bef30Auba, C. (Cristina)|||/items/e35d9621-fca6-477a-b9f2-198573b0e8daMelero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4eRouzaut, A. (Ana)|||/items/4cb4f93a-048e-4093-a125-f987ff4b9024Draining lymph nodesT-lymphocyteHomotypic cell-adhesionICAM-1Immune responseCancer immunotherapyThe quantity of T-lymphocytes reaching the draining lymph nodes from tumors is likely important to mount effective distant responses and for the establishment of long term systemic memory. Looking into mechanisms behind lymphocyte egress, we directed our attention to leukocyte adhesion mechanisms inside tumors. Here we demonstrate that activated T-cells form intra-tumor aggregates in a LFA-1-ICAM-1-dependent fashion in mouse models of melanoma and breast cancer. We also provide evidence of the presence of T-cell clusters in primary human melanoma. Disruption of LFA-1-ICAM-1 interactions, and thereby T-cell clustering, enhances the arrival of activated CD8+ T-cells to tumor draining lymph nodes in both transplanted and spontaneous cancer models. Interestingly, upon ICAM-1 blockade, the expression of the chemotactic receptor CCR7 augments in tumor infiltrating lymphocytes and in in-vitro de-clustered T cells, as well as their ability to transmigrate across lymphatic endothelial cells. We propose that ICAM-1-mediated homotypic T-lymphocyte aggregation may serve as a tumor-mediated immune retention mechanism entrapping activated CD8+ T cells in the tumor microenvironment. Modulation of T-cell adhesion may be of use to improve the transit of activated lymphocytes toward the lymph nodes and their subsequent recirculation.Frontiers MediaDadun. Depósito Académico Digital Universidad de Navarra20192019-03-2120182018-09-1220182018-09-12journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/56647reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Universidad de NavarraInglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/566472026-06-21T12:47:57Z
dc.title.none.fl_str_mv ICAM-1-LFA-1 dependent CD8+ T-Lymphocyte aggregation in tumor tissue prevents recirculation to draining lymph nodes
title ICAM-1-LFA-1 dependent CD8+ T-Lymphocyte aggregation in tumor tissue prevents recirculation to draining lymph nodes
spellingShingle ICAM-1-LFA-1 dependent CD8+ T-Lymphocyte aggregation in tumor tissue prevents recirculation to draining lymph nodes
Yanguas, A. (Alba)|||/items/7fd085ff-f8b5-4d04-beb0-44d2c5a45f19
Draining lymph nodes
T-lymphocyte
Homotypic cell-adhesion
ICAM-1
Immune response
Cancer immunotherapy
title_short ICAM-1-LFA-1 dependent CD8+ T-Lymphocyte aggregation in tumor tissue prevents recirculation to draining lymph nodes
title_full ICAM-1-LFA-1 dependent CD8+ T-Lymphocyte aggregation in tumor tissue prevents recirculation to draining lymph nodes
title_fullStr ICAM-1-LFA-1 dependent CD8+ T-Lymphocyte aggregation in tumor tissue prevents recirculation to draining lymph nodes
title_full_unstemmed ICAM-1-LFA-1 dependent CD8+ T-Lymphocyte aggregation in tumor tissue prevents recirculation to draining lymph nodes
title_sort ICAM-1-LFA-1 dependent CD8+ T-Lymphocyte aggregation in tumor tissue prevents recirculation to draining lymph nodes
dc.creator.none.fl_str_mv Yanguas, A. (Alba)|||/items/7fd085ff-f8b5-4d04-beb0-44d2c5a45f19
Garasa, S. (Saray)|||/items/51924af8-57aa-477c-b3d8-886422be3713
Teijeira-Sánchez, A. (Álvaro)|||/items/8a954ec4-8458-46ea-b8e6-3165119bef30
Auba, C. (Cristina)|||/items/e35d9621-fca6-477a-b9f2-198573b0e8da
Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4e
Rouzaut, A. (Ana)|||/items/4cb4f93a-048e-4093-a125-f987ff4b9024
author Yanguas, A. (Alba)|||/items/7fd085ff-f8b5-4d04-beb0-44d2c5a45f19
author_facet Yanguas, A. (Alba)|||/items/7fd085ff-f8b5-4d04-beb0-44d2c5a45f19
Garasa, S. (Saray)|||/items/51924af8-57aa-477c-b3d8-886422be3713
Teijeira-Sánchez, A. (Álvaro)|||/items/8a954ec4-8458-46ea-b8e6-3165119bef30
Auba, C. (Cristina)|||/items/e35d9621-fca6-477a-b9f2-198573b0e8da
Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4e
Rouzaut, A. (Ana)|||/items/4cb4f93a-048e-4093-a125-f987ff4b9024
author_role author
author2 Garasa, S. (Saray)|||/items/51924af8-57aa-477c-b3d8-886422be3713
Teijeira-Sánchez, A. (Álvaro)|||/items/8a954ec4-8458-46ea-b8e6-3165119bef30
Auba, C. (Cristina)|||/items/e35d9621-fca6-477a-b9f2-198573b0e8da
Melero, I. (Ignacio)|||/items/82113ea8-7ce1-49d5-9ee3-42cf20db1c4e
Rouzaut, A. (Ana)|||/items/4cb4f93a-048e-4093-a125-f987ff4b9024
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv Draining lymph nodes
T-lymphocyte
Homotypic cell-adhesion
ICAM-1
Immune response
Cancer immunotherapy
topic Draining lymph nodes
T-lymphocyte
Homotypic cell-adhesion
ICAM-1
Immune response
Cancer immunotherapy
description The quantity of T-lymphocytes reaching the draining lymph nodes from tumors is likely important to mount effective distant responses and for the establishment of long term systemic memory. Looking into mechanisms behind lymphocyte egress, we directed our attention to leukocyte adhesion mechanisms inside tumors. Here we demonstrate that activated T-cells form intra-tumor aggregates in a LFA-1-ICAM-1-dependent fashion in mouse models of melanoma and breast cancer. We also provide evidence of the presence of T-cell clusters in primary human melanoma. Disruption of LFA-1-ICAM-1 interactions, and thereby T-cell clustering, enhances the arrival of activated CD8+ T-cells to tumor draining lymph nodes in both transplanted and spontaneous cancer models. Interestingly, upon ICAM-1 blockade, the expression of the chemotactic receptor CCR7 augments in tumor infiltrating lymphocytes and in in-vitro de-clustered T cells, as well as their ability to transmigrate across lymphatic endothelial cells. We propose that ICAM-1-mediated homotypic T-lymphocyte aggregation may serve as a tumor-mediated immune retention mechanism entrapping activated CD8+ T cells in the tumor microenvironment. Modulation of T-cell adhesion may be of use to improve the transit of activated lymphocytes toward the lymph nodes and their subsequent recirculation.
publishDate 2018
dc.date.none.fl_str_mv 2018
2018-09-12
2018
2018-09-12
2019
2019-03-21
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10171/56647
url https://hdl.handle.net/10171/56647
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Frontiers Media
publisher.none.fl_str_mv Frontiers Media
dc.source.none.fl_str_mv reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra
instname:Universidad de Navarra
instname_str Universidad de Navarra
reponame_str Dadun. Depósito Académico Digital de la Universidad de Navarra
collection Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.300724

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