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Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer

The exact nature and dynamics of pancreatic ductal adenocarcinoma (PDAC) immune composition remains largely unknown. Desmoplasia is suggested to polarize PDAC immunity. Therefore, a comprehensive evaluation of the composition and distribution of desmoplastic elements and T-cell infiltration is neces...

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Autores principales: Carstens, Julienne L., Correa de Sampaio, Pedro, Yang, Dalu, Barua, Souptik, Wang, Huamin, Rao, Arvind, Allison, James P., LeBleu, Valerie S., Kalluri, Raghu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414182/
https://www.ncbi.nlm.nih.gov/pubmed/28447602
http://dx.doi.org/10.1038/ncomms15095
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author Carstens, Julienne L.
Correa de Sampaio, Pedro
Yang, Dalu
Barua, Souptik
Wang, Huamin
Rao, Arvind
Allison, James P.
LeBleu, Valerie S.
Kalluri, Raghu
author_facet Carstens, Julienne L.
Correa de Sampaio, Pedro
Yang, Dalu
Barua, Souptik
Wang, Huamin
Rao, Arvind
Allison, James P.
LeBleu, Valerie S.
Kalluri, Raghu
author_sort Carstens, Julienne L.
collection PubMed
description The exact nature and dynamics of pancreatic ductal adenocarcinoma (PDAC) immune composition remains largely unknown. Desmoplasia is suggested to polarize PDAC immunity. Therefore, a comprehensive evaluation of the composition and distribution of desmoplastic elements and T-cell infiltration is necessary to delineate their roles. Here we develop a novel computational imaging technology for the simultaneous evaluation of eight distinct markers, allowing for spatial analysis of distinct populations within the same section. We report a heterogeneous population of infiltrating T lymphocytes. Spatial distribution of cytotoxic T cells in proximity to cancer cells correlates with increased overall patient survival. Collagen-I and αSMA(+) fibroblasts do not correlate with paucity in T-cell accumulation, suggesting that PDAC desmoplasia may not be a simple physical barrier. Further exploration of this technology may improve our understanding of how specific stromal composition could impact T-cell activity, with potential impact on the optimization of immune-modulatory therapies.
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spelling pubmed-54141822017-05-17 Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer Carstens, Julienne L. Correa de Sampaio, Pedro Yang, Dalu Barua, Souptik Wang, Huamin Rao, Arvind Allison, James P. LeBleu, Valerie S. Kalluri, Raghu Nat Commun Article The exact nature and dynamics of pancreatic ductal adenocarcinoma (PDAC) immune composition remains largely unknown. Desmoplasia is suggested to polarize PDAC immunity. Therefore, a comprehensive evaluation of the composition and distribution of desmoplastic elements and T-cell infiltration is necessary to delineate their roles. Here we develop a novel computational imaging technology for the simultaneous evaluation of eight distinct markers, allowing for spatial analysis of distinct populations within the same section. We report a heterogeneous population of infiltrating T lymphocytes. Spatial distribution of cytotoxic T cells in proximity to cancer cells correlates with increased overall patient survival. Collagen-I and αSMA(+) fibroblasts do not correlate with paucity in T-cell accumulation, suggesting that PDAC desmoplasia may not be a simple physical barrier. Further exploration of this technology may improve our understanding of how specific stromal composition could impact T-cell activity, with potential impact on the optimization of immune-modulatory therapies. Nature Publishing Group 2017-04-27 /pmc/articles/PMC5414182/ /pubmed/28447602 http://dx.doi.org/10.1038/ncomms15095 Text en Copyright © 2017, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Carstens, Julienne L.
Correa de Sampaio, Pedro
Yang, Dalu
Barua, Souptik
Wang, Huamin
Rao, Arvind
Allison, James P.
LeBleu, Valerie S.
Kalluri, Raghu
Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer
title Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer
title_full Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer
title_fullStr Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer
title_full_unstemmed Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer
title_short Spatial computation of intratumoral T cells correlates with survival of patients with pancreatic cancer
title_sort spatial computation of intratumoral t cells correlates with survival of patients with pancreatic cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414182/
https://www.ncbi.nlm.nih.gov/pubmed/28447602
http://dx.doi.org/10.1038/ncomms15095
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