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High CD8(+) and absence of Foxp3(+) T lymphocytes infiltration in gallbladder tumors correlate with prolonged patients survival

BACKGROUND: Gallbladder cancer (GBC), although infrequent in industrialized countries, has high incidence rates in certain world regions, being a leading cause of death among elderly Chilean women. Surgery is the only effective treatment, and a five-year survival rate of advanced-stage patients is l...

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Autores principales: Fluxá, Paula, Rojas-Sepúlveda, Daniel, Gleisner, María Alejandra, Tittarelli, Andrés, Villegas, Pablo, Tapia, Loreto, Rivera, María Teresa, López, Mercedes Natalia, Catán, Felipe, Uribe, Mario, Salazar-Onfray, Flavio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833069/
https://www.ncbi.nlm.nih.gov/pubmed/29499656
http://dx.doi.org/10.1186/s12885-018-4147-6
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author Fluxá, Paula
Rojas-Sepúlveda, Daniel
Gleisner, María Alejandra
Tittarelli, Andrés
Villegas, Pablo
Tapia, Loreto
Rivera, María Teresa
López, Mercedes Natalia
Catán, Felipe
Uribe, Mario
Salazar-Onfray, Flavio
author_facet Fluxá, Paula
Rojas-Sepúlveda, Daniel
Gleisner, María Alejandra
Tittarelli, Andrés
Villegas, Pablo
Tapia, Loreto
Rivera, María Teresa
López, Mercedes Natalia
Catán, Felipe
Uribe, Mario
Salazar-Onfray, Flavio
author_sort Fluxá, Paula
collection PubMed
description BACKGROUND: Gallbladder cancer (GBC), although infrequent in industrialized countries, has high incidence rates in certain world regions, being a leading cause of death among elderly Chilean women. Surgery is the only effective treatment, and a five-year survival rate of advanced-stage patients is less than 10%. Hence, exploring immunotherapy is relevant, although GBC immunogenicity is poorly understood. This study examined the relationship between the host immune response and GBC patient survival based on the presence of tumor-infiltrating lymphocytes at different disease stages. METHODS: Tumor tissues from 80 GBC patients were analyzed by immunohistochemistry for the presence of CD3(+), CD4(+), CD8(+), and Foxp3(+) T cell populations, and the results were associated with clinical stage and patient survival. RESULTS: The majority of tumor samples showed CD3(+) T cell infiltration, which correlated with better prognosis, particularly in advanced disease stages. CD8(+), but not CD4(+), T cell infiltration correlated with improved survival, particularly in advanced disease stages. Interestingly, a < 1 CD4(+)/CD8(+) T cell ratio was related with increased survival. Additionally, the presence of Foxp3(+) T cells correlated with decreased patient survival, whereas a ≤ 1 Foxp3(+)/CD8(+) T cell ratio was associated with improved patient survival. CONCLUSIONS: Depending on the disease stage, the presence of CD8(+) and absence of Foxp3(+) T cell populations in tumor tissues correlated with improved GBC patient survival, and thus represent potential markers for prognosis and management of advanced disease, and supports testing of immunotherapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4147-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-58330692018-03-05 High CD8(+) and absence of Foxp3(+) T lymphocytes infiltration in gallbladder tumors correlate with prolonged patients survival Fluxá, Paula Rojas-Sepúlveda, Daniel Gleisner, María Alejandra Tittarelli, Andrés Villegas, Pablo Tapia, Loreto Rivera, María Teresa López, Mercedes Natalia Catán, Felipe Uribe, Mario Salazar-Onfray, Flavio BMC Cancer Research Article BACKGROUND: Gallbladder cancer (GBC), although infrequent in industrialized countries, has high incidence rates in certain world regions, being a leading cause of death among elderly Chilean women. Surgery is the only effective treatment, and a five-year survival rate of advanced-stage patients is less than 10%. Hence, exploring immunotherapy is relevant, although GBC immunogenicity is poorly understood. This study examined the relationship between the host immune response and GBC patient survival based on the presence of tumor-infiltrating lymphocytes at different disease stages. METHODS: Tumor tissues from 80 GBC patients were analyzed by immunohistochemistry for the presence of CD3(+), CD4(+), CD8(+), and Foxp3(+) T cell populations, and the results were associated with clinical stage and patient survival. RESULTS: The majority of tumor samples showed CD3(+) T cell infiltration, which correlated with better prognosis, particularly in advanced disease stages. CD8(+), but not CD4(+), T cell infiltration correlated with improved survival, particularly in advanced disease stages. Interestingly, a < 1 CD4(+)/CD8(+) T cell ratio was related with increased survival. Additionally, the presence of Foxp3(+) T cells correlated with decreased patient survival, whereas a ≤ 1 Foxp3(+)/CD8(+) T cell ratio was associated with improved patient survival. CONCLUSIONS: Depending on the disease stage, the presence of CD8(+) and absence of Foxp3(+) T cell populations in tumor tissues correlated with improved GBC patient survival, and thus represent potential markers for prognosis and management of advanced disease, and supports testing of immunotherapy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12885-018-4147-6) contains supplementary material, which is available to authorized users. BioMed Central 2018-03-02 /pmc/articles/PMC5833069/ /pubmed/29499656 http://dx.doi.org/10.1186/s12885-018-4147-6 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Fluxá, Paula
Rojas-Sepúlveda, Daniel
Gleisner, María Alejandra
Tittarelli, Andrés
Villegas, Pablo
Tapia, Loreto
Rivera, María Teresa
López, Mercedes Natalia
Catán, Felipe
Uribe, Mario
Salazar-Onfray, Flavio
High CD8(+) and absence of Foxp3(+) T lymphocytes infiltration in gallbladder tumors correlate with prolonged patients survival
title High CD8(+) and absence of Foxp3(+) T lymphocytes infiltration in gallbladder tumors correlate with prolonged patients survival
title_full High CD8(+) and absence of Foxp3(+) T lymphocytes infiltration in gallbladder tumors correlate with prolonged patients survival
title_fullStr High CD8(+) and absence of Foxp3(+) T lymphocytes infiltration in gallbladder tumors correlate with prolonged patients survival
title_full_unstemmed High CD8(+) and absence of Foxp3(+) T lymphocytes infiltration in gallbladder tumors correlate with prolonged patients survival
title_short High CD8(+) and absence of Foxp3(+) T lymphocytes infiltration in gallbladder tumors correlate with prolonged patients survival
title_sort high cd8(+) and absence of foxp3(+) t lymphocytes infiltration in gallbladder tumors correlate with prolonged patients survival
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833069/
https://www.ncbi.nlm.nih.gov/pubmed/29499656
http://dx.doi.org/10.1186/s12885-018-4147-6
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