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Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma

BACKGROUND: Both activated tumor-infiltrating lymphocytes (TILs) and immune-suppressive cells, such as regulatory T cells (Tregs), in the tumor microenvironment (TME) play an important role in the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: The densities of TILs, pro...

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Autores principales: Kiryu, Sachie, Ito, Zensho, Suka, Machi, Bito, Tsuuse, Kan, Shin, Uchiyama, Kan, Saruta, Masayuki, Hata, Taigo, Takano, Yuki, Fujioka, Shuichi, Misawa, Takeyuki, Yamauchi, Takashi, Yanagisawa, Hiroyuki, Sato, Nobuhiro, Ohkusa, Toshifumi, Sugiyama, Haruo, Koido, Shigeo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582170/
https://www.ncbi.nlm.nih.gov/pubmed/34758773
http://dx.doi.org/10.1186/s12885-021-08911-4
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author Kiryu, Sachie
Ito, Zensho
Suka, Machi
Bito, Tsuuse
Kan, Shin
Uchiyama, Kan
Saruta, Masayuki
Hata, Taigo
Takano, Yuki
Fujioka, Shuichi
Misawa, Takeyuki
Yamauchi, Takashi
Yanagisawa, Hiroyuki
Sato, Nobuhiro
Ohkusa, Toshifumi
Sugiyama, Haruo
Koido, Shigeo
author_facet Kiryu, Sachie
Ito, Zensho
Suka, Machi
Bito, Tsuuse
Kan, Shin
Uchiyama, Kan
Saruta, Masayuki
Hata, Taigo
Takano, Yuki
Fujioka, Shuichi
Misawa, Takeyuki
Yamauchi, Takashi
Yanagisawa, Hiroyuki
Sato, Nobuhiro
Ohkusa, Toshifumi
Sugiyama, Haruo
Koido, Shigeo
author_sort Kiryu, Sachie
collection PubMed
description BACKGROUND: Both activated tumor-infiltrating lymphocytes (TILs) and immune-suppressive cells, such as regulatory T cells (Tregs), in the tumor microenvironment (TME) play an important role in the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: The densities of TILs, programmed death receptor 1 (PD-1) + T cells, and forkhead box P3 (Foxp3) + T cells were analyzed by immunohistochemical staining. The associations of the immunological status of the PDAC microenvironment with overall survival (OS) time and disease-free survival (DFS) time were evaluated. RESULTS: PDAC patients with a high density of TILs in the TME or PD-1-positive T cells in tertiary lymphoid aggregates (TLAs) demonstrated a significantly better prognosis than those with a low density of TILs or PD-1-negativity, respectively. Moreover, PDAC patients with high levels of Foxp3-expressing T cells showed a worse prognosis than those with low levels of Foxp3-expressing T cells. Importantly, even with a high density of the TILs in TME or PD-1-positive T cells in TLAs, PDAC patients with high levels of Foxp3-expressing T cells showed a worse prognosis than patients with low levels of Foxp3-expressing T cells. A PDAC TME with a high density of TILs/high PD-1 positivity/low Foxp3 expression was an independent predictive marker associated with superior prognosis. CONCLUSION: Combined assessment of TILs, PD-1+ cells, and Foxp3+ T cells in the TME may predict the prognosis of PDAC patients following surgical resection. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08911-4.
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spelling pubmed-85821702021-11-15 Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma Kiryu, Sachie Ito, Zensho Suka, Machi Bito, Tsuuse Kan, Shin Uchiyama, Kan Saruta, Masayuki Hata, Taigo Takano, Yuki Fujioka, Shuichi Misawa, Takeyuki Yamauchi, Takashi Yanagisawa, Hiroyuki Sato, Nobuhiro Ohkusa, Toshifumi Sugiyama, Haruo Koido, Shigeo BMC Cancer Research BACKGROUND: Both activated tumor-infiltrating lymphocytes (TILs) and immune-suppressive cells, such as regulatory T cells (Tregs), in the tumor microenvironment (TME) play an important role in the prognosis of patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: The densities of TILs, programmed death receptor 1 (PD-1) + T cells, and forkhead box P3 (Foxp3) + T cells were analyzed by immunohistochemical staining. The associations of the immunological status of the PDAC microenvironment with overall survival (OS) time and disease-free survival (DFS) time were evaluated. RESULTS: PDAC patients with a high density of TILs in the TME or PD-1-positive T cells in tertiary lymphoid aggregates (TLAs) demonstrated a significantly better prognosis than those with a low density of TILs or PD-1-negativity, respectively. Moreover, PDAC patients with high levels of Foxp3-expressing T cells showed a worse prognosis than those with low levels of Foxp3-expressing T cells. Importantly, even with a high density of the TILs in TME or PD-1-positive T cells in TLAs, PDAC patients with high levels of Foxp3-expressing T cells showed a worse prognosis than patients with low levels of Foxp3-expressing T cells. A PDAC TME with a high density of TILs/high PD-1 positivity/low Foxp3 expression was an independent predictive marker associated with superior prognosis. CONCLUSION: Combined assessment of TILs, PD-1+ cells, and Foxp3+ T cells in the TME may predict the prognosis of PDAC patients following surgical resection. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-08911-4. BioMed Central 2021-11-10 /pmc/articles/PMC8582170/ /pubmed/34758773 http://dx.doi.org/10.1186/s12885-021-08911-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Kiryu, Sachie
Ito, Zensho
Suka, Machi
Bito, Tsuuse
Kan, Shin
Uchiyama, Kan
Saruta, Masayuki
Hata, Taigo
Takano, Yuki
Fujioka, Shuichi
Misawa, Takeyuki
Yamauchi, Takashi
Yanagisawa, Hiroyuki
Sato, Nobuhiro
Ohkusa, Toshifumi
Sugiyama, Haruo
Koido, Shigeo
Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma
title Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma
title_full Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma
title_fullStr Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma
title_full_unstemmed Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma
title_short Prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma
title_sort prognostic value of immune factors in the tumor microenvironment of patients with pancreatic ductal adenocarcinoma
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582170/
https://www.ncbi.nlm.nih.gov/pubmed/34758773
http://dx.doi.org/10.1186/s12885-021-08911-4
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