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KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling

SIMPLE SUMMARY: Killer-cell immunoglobulin-like receptors (KIR) are molecules expressed by the most important cells of the immune system for cancer immune vigilance, natural killer (NK) and effector T cells. In this manuscript we study the role that cytotoxic CD8+ T cells expressing KIR receptors co...

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Autores principales: Gimeno, Lourdes, Serrano-López, Emilio M., Campillo, José A., Cánovas-Zapata, María A., Acuña, Omar S., García-Cózar, Francisco, Martínez-Sánchez, María V., Martínez-Hernández, María D., Soto-Ramírez, María F., López-Cubillana, Pedro, Martínez-Escribano, Jorge, Martínez-García, Jerónimo, Corbalan-García, Senena, Álvarez-López, María R., Minguela, Alfredo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650600/
https://www.ncbi.nlm.nih.gov/pubmed/33076479
http://dx.doi.org/10.3390/cancers12102991
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author Gimeno, Lourdes
Serrano-López, Emilio M.
Campillo, José A.
Cánovas-Zapata, María A.
Acuña, Omar S.
García-Cózar, Francisco
Martínez-Sánchez, María V.
Martínez-Hernández, María D.
Soto-Ramírez, María F.
López-Cubillana, Pedro
Martínez-Escribano, Jorge
Martínez-García, Jerónimo
Corbalan-García, Senena
Álvarez-López, María R.
Minguela, Alfredo
author_facet Gimeno, Lourdes
Serrano-López, Emilio M.
Campillo, José A.
Cánovas-Zapata, María A.
Acuña, Omar S.
García-Cózar, Francisco
Martínez-Sánchez, María V.
Martínez-Hernández, María D.
Soto-Ramírez, María F.
López-Cubillana, Pedro
Martínez-Escribano, Jorge
Martínez-García, Jerónimo
Corbalan-García, Senena
Álvarez-López, María R.
Minguela, Alfredo
author_sort Gimeno, Lourdes
collection PubMed
description SIMPLE SUMMARY: Killer-cell immunoglobulin-like receptors (KIR) are molecules expressed by the most important cells of the immune system for cancer immune vigilance, natural killer (NK) and effector T cells. In this manuscript we study the role that cytotoxic CD8+ T cells expressing KIR receptors could play in cancer immune surveillance. With this objective, frequencies of different KIR+ CD8+ T cell subsets are correlated with the overall survival of patients with melanoma, ovarian and bladder carcinomas. In addition, the gene expression profile of KIR+ CD8+ T cell subsets related to the survival of patients is studied with the aim of discovering new therapeutic targets, so that the outcome of patients with cancer can be improved. ABSTRACT: Killer-cell immunoglobulin-like receptors (KIR) are expressed by natural killer (NK) and effector T cells. Although KIR+ T cells accumulate in oncologic patients, their role in cancer immune response remains elusive. This study explored the role of KIR+CD8+ T cells in cancer immunosurveillance by analyzing their frequency at diagnosis in the blood of 249 patients (80 melanomas, 80 bladder cancers, and 89 ovarian cancers), their relationship with overall survival (OS) of patients, and their gene expression profiles. KIR2DL1+ CD8+ T cells expanded in the presence of HLA-C2-ligands in patients who survived, but it did not in patients who died. In contrast, presence of HLA-C1-ligands was associated with dose-dependent expansions of KIR2DL2/S2+ CD8+ T cells and with shorter OS. KIR interactions with their specific ligands profoundly impacted CD8+ T cell expression profiles, involving multiple signaling pathways, effector functions, the secretome, and consequently, the cellular microenvironment, which could impact their cancer immunosurveillance capacities. KIR2DL1/S1+ CD8+ T cells showed a gene expression signature related to efficient tumor immunosurveillance, whereas KIR2DL2/L3/S2+CD8+ T cells showed transcriptomic profiles related to suppressive anti-tumor responses. These results could be the basis for the discovery of new therapeutic targets so that the outcome of patients with cancer can be improved.
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spelling pubmed-76506002020-11-10 KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling Gimeno, Lourdes Serrano-López, Emilio M. Campillo, José A. Cánovas-Zapata, María A. Acuña, Omar S. García-Cózar, Francisco Martínez-Sánchez, María V. Martínez-Hernández, María D. Soto-Ramírez, María F. López-Cubillana, Pedro Martínez-Escribano, Jorge Martínez-García, Jerónimo Corbalan-García, Senena Álvarez-López, María R. Minguela, Alfredo Cancers (Basel) Article SIMPLE SUMMARY: Killer-cell immunoglobulin-like receptors (KIR) are molecules expressed by the most important cells of the immune system for cancer immune vigilance, natural killer (NK) and effector T cells. In this manuscript we study the role that cytotoxic CD8+ T cells expressing KIR receptors could play in cancer immune surveillance. With this objective, frequencies of different KIR+ CD8+ T cell subsets are correlated with the overall survival of patients with melanoma, ovarian and bladder carcinomas. In addition, the gene expression profile of KIR+ CD8+ T cell subsets related to the survival of patients is studied with the aim of discovering new therapeutic targets, so that the outcome of patients with cancer can be improved. ABSTRACT: Killer-cell immunoglobulin-like receptors (KIR) are expressed by natural killer (NK) and effector T cells. Although KIR+ T cells accumulate in oncologic patients, their role in cancer immune response remains elusive. This study explored the role of KIR+CD8+ T cells in cancer immunosurveillance by analyzing their frequency at diagnosis in the blood of 249 patients (80 melanomas, 80 bladder cancers, and 89 ovarian cancers), their relationship with overall survival (OS) of patients, and their gene expression profiles. KIR2DL1+ CD8+ T cells expanded in the presence of HLA-C2-ligands in patients who survived, but it did not in patients who died. In contrast, presence of HLA-C1-ligands was associated with dose-dependent expansions of KIR2DL2/S2+ CD8+ T cells and with shorter OS. KIR interactions with their specific ligands profoundly impacted CD8+ T cell expression profiles, involving multiple signaling pathways, effector functions, the secretome, and consequently, the cellular microenvironment, which could impact their cancer immunosurveillance capacities. KIR2DL1/S1+ CD8+ T cells showed a gene expression signature related to efficient tumor immunosurveillance, whereas KIR2DL2/L3/S2+CD8+ T cells showed transcriptomic profiles related to suppressive anti-tumor responses. These results could be the basis for the discovery of new therapeutic targets so that the outcome of patients with cancer can be improved. MDPI 2020-10-15 /pmc/articles/PMC7650600/ /pubmed/33076479 http://dx.doi.org/10.3390/cancers12102991 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
Gimeno, Lourdes
Serrano-López, Emilio M.
Campillo, José A.
Cánovas-Zapata, María A.
Acuña, Omar S.
García-Cózar, Francisco
Martínez-Sánchez, María V.
Martínez-Hernández, María D.
Soto-Ramírez, María F.
López-Cubillana, Pedro
Martínez-Escribano, Jorge
Martínez-García, Jerónimo
Corbalan-García, Senena
Álvarez-López, María R.
Minguela, Alfredo
KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling
title KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling
title_full KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling
title_fullStr KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling
title_full_unstemmed KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling
title_short KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling
title_sort kir+ cd8+ t lymphocytes in cancer immunosurveillance and patient survival: gene expression profiling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7650600/
https://www.ncbi.nlm.nih.gov/pubmed/33076479
http://dx.doi.org/10.3390/cancers12102991
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