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CCL19 reduces tumour burden in a model of advanced lung cancer

Epstein–Barr virus-induced molecule 1 ligand chemokine (CCL19) is a CC chemokine that chemoattracts both dendritic cells (DC) and T lymphocytes. We evaluated the antitumour efficacy of CCL19 in a murine model of spontaneous bronchoalveolar cell carcinoma. These transgenic mice (CC-10 TAg) express th...

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Autores principales: Hillinger, S, Yang, S-C, Batra, R K, Strieter, R M, Weder, W, Dubinett, S M, Sharma, S
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361223/
https://www.ncbi.nlm.nih.gov/pubmed/16598185
http://dx.doi.org/10.1038/sj.bjc.6603061
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author Hillinger, S
Yang, S-C
Batra, R K
Strieter, R M
Weder, W
Dubinett, S M
Sharma, S
author_facet Hillinger, S
Yang, S-C
Batra, R K
Strieter, R M
Weder, W
Dubinett, S M
Sharma, S
author_sort Hillinger, S
collection PubMed
description Epstein–Barr virus-induced molecule 1 ligand chemokine (CCL19) is a CC chemokine that chemoattracts both dendritic cells (DC) and T lymphocytes. We evaluated the antitumour efficacy of CCL19 in a murine model of spontaneous bronchoalveolar cell carcinoma. These transgenic mice (CC-10 TAg) express the SV40 large T antigen under the Clara Cell promoter, develop bilateral, multifocal, pulmonary carcinomas and die at 4 months owing to progressive pulmonary tumour burden. To mimic therapy in late-stage disease, 3-month-old transgenic mice were treated with recombinant CCL19 (0.5 μg dose(−1)) by intranodal (axillary lymph node region) injection three times per week for 4 weeks. CCL19 treatment led to a marked reduction in tumour burden with extensive mononuclear infiltration of the tumours compared to diluent treated controls. Flow cytometric analyses showed significant increases in CD4 and CD8T cell subsets as well as DC in the lungs of CCL19-treated mice. Lung tissue cytokine profiles showed a shift towards immune stimulatory molecules with a decrease in the immunosuppressive cytokine TGF-β. Our findings show that CCL19 may serve as a potential immune stimulator and provide a strong rationale for the evaluation of CCL19 in cancer immunotherapy.
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spelling pubmed-23612232009-09-10 CCL19 reduces tumour burden in a model of advanced lung cancer Hillinger, S Yang, S-C Batra, R K Strieter, R M Weder, W Dubinett, S M Sharma, S Br J Cancer Translational Therapeutics Epstein–Barr virus-induced molecule 1 ligand chemokine (CCL19) is a CC chemokine that chemoattracts both dendritic cells (DC) and T lymphocytes. We evaluated the antitumour efficacy of CCL19 in a murine model of spontaneous bronchoalveolar cell carcinoma. These transgenic mice (CC-10 TAg) express the SV40 large T antigen under the Clara Cell promoter, develop bilateral, multifocal, pulmonary carcinomas and die at 4 months owing to progressive pulmonary tumour burden. To mimic therapy in late-stage disease, 3-month-old transgenic mice were treated with recombinant CCL19 (0.5 μg dose(−1)) by intranodal (axillary lymph node region) injection three times per week for 4 weeks. CCL19 treatment led to a marked reduction in tumour burden with extensive mononuclear infiltration of the tumours compared to diluent treated controls. Flow cytometric analyses showed significant increases in CD4 and CD8T cell subsets as well as DC in the lungs of CCL19-treated mice. Lung tissue cytokine profiles showed a shift towards immune stimulatory molecules with a decrease in the immunosuppressive cytokine TGF-β. Our findings show that CCL19 may serve as a potential immune stimulator and provide a strong rationale for the evaluation of CCL19 in cancer immunotherapy. Nature Publishing Group 2006-04-10 2006-04-04 /pmc/articles/PMC2361223/ /pubmed/16598185 http://dx.doi.org/10.1038/sj.bjc.6603061 Text en Copyright © 2006 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Translational Therapeutics
Hillinger, S
Yang, S-C
Batra, R K
Strieter, R M
Weder, W
Dubinett, S M
Sharma, S
CCL19 reduces tumour burden in a model of advanced lung cancer
title CCL19 reduces tumour burden in a model of advanced lung cancer
title_full CCL19 reduces tumour burden in a model of advanced lung cancer
title_fullStr CCL19 reduces tumour burden in a model of advanced lung cancer
title_full_unstemmed CCL19 reduces tumour burden in a model of advanced lung cancer
title_short CCL19 reduces tumour burden in a model of advanced lung cancer
title_sort ccl19 reduces tumour burden in a model of advanced lung cancer
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2361223/
https://www.ncbi.nlm.nih.gov/pubmed/16598185
http://dx.doi.org/10.1038/sj.bjc.6603061
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