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Regulatory T Cells and Tumor-Associated Macrophages in the Tumor Microenvironment in Non-Muscle Invasive Bladder Cancer Treated with Intravesical Bacille Calmette-Guérin: A Long-Term Follow-Up Study of a Japanese Cohort

The clinical significance of regulatory T cells (Treg) and tumor-associated macrophages (TAM) in the tumor microenvironment of human bladder cancer remains unclear. The aim of this study is to explore their relevance to oncological features in non-muscle invasive bladder cancer (NMIBC). We carried o...

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Autores principales: Miyake, Makito, Tatsumi, Yoshihiro, Gotoh, Daisuke, Ohnishi, Sayuri, Owari, Takuya, Iida, Kota, Ohnishi, Kenta, Hori, Shunta, Morizawa, Yosuke, Itami, Yoshitaka, Nakai, Yasushi, Inoue, Takeshi, Anai, Satoshi, Torimoto, Kazumasa, Aoki, Katsuya, Shimada, Keiji, Konishi, Noboru, Tanaka, Nobumichi, Fujimoto, Kiyohide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666867/
https://www.ncbi.nlm.nih.gov/pubmed/29048388
http://dx.doi.org/10.3390/ijms18102186
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author Miyake, Makito
Tatsumi, Yoshihiro
Gotoh, Daisuke
Ohnishi, Sayuri
Owari, Takuya
Iida, Kota
Ohnishi, Kenta
Hori, Shunta
Morizawa, Yosuke
Itami, Yoshitaka
Nakai, Yasushi
Inoue, Takeshi
Anai, Satoshi
Torimoto, Kazumasa
Aoki, Katsuya
Shimada, Keiji
Konishi, Noboru
Tanaka, Nobumichi
Fujimoto, Kiyohide
author_facet Miyake, Makito
Tatsumi, Yoshihiro
Gotoh, Daisuke
Ohnishi, Sayuri
Owari, Takuya
Iida, Kota
Ohnishi, Kenta
Hori, Shunta
Morizawa, Yosuke
Itami, Yoshitaka
Nakai, Yasushi
Inoue, Takeshi
Anai, Satoshi
Torimoto, Kazumasa
Aoki, Katsuya
Shimada, Keiji
Konishi, Noboru
Tanaka, Nobumichi
Fujimoto, Kiyohide
author_sort Miyake, Makito
collection PubMed
description The clinical significance of regulatory T cells (Treg) and tumor-associated macrophages (TAM) in the tumor microenvironment of human bladder cancer remains unclear. The aim of this study is to explore their relevance to oncological features in non-muscle invasive bladder cancer (NMIBC). We carried out immunohistochemical analysis of forkhead box P3 (FOXP3, Treg maker), CD204 (TAM marker), and interleukin-6 (IL6) using surgical specimens obtained from 154 NMIBC patients. The Treg and TAM counts surrounding the cancer lesion and IL6-positive cancer cell counts were evaluated against clinicopathological variables. We focused on the ability of the Treg and TAM counts around the cancer lesion to predict outcomes after adjuvant intravesical Bacille Calmette–Guérin (BCG) treatment. High Treg counts were associated with female patients, older age, T1 category, and high tumor grade. TAM count was significantly correlated with Treg count and with IL6-positive cancer cell count. In our analysis of 71 patients treated with BCG, high counts of Treg and TAM were associated with shorter recurrence-free survival, and the former was an independent predictor of recurrence. Poor response to intravesical BCG was associated with Treg and TAM in the tumor microenvironment. Disrupting the immune network can be a supplementary therapeutic approach for NMIBC patients receiving intravesical BCG.
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spelling pubmed-56668672017-11-09 Regulatory T Cells and Tumor-Associated Macrophages in the Tumor Microenvironment in Non-Muscle Invasive Bladder Cancer Treated with Intravesical Bacille Calmette-Guérin: A Long-Term Follow-Up Study of a Japanese Cohort Miyake, Makito Tatsumi, Yoshihiro Gotoh, Daisuke Ohnishi, Sayuri Owari, Takuya Iida, Kota Ohnishi, Kenta Hori, Shunta Morizawa, Yosuke Itami, Yoshitaka Nakai, Yasushi Inoue, Takeshi Anai, Satoshi Torimoto, Kazumasa Aoki, Katsuya Shimada, Keiji Konishi, Noboru Tanaka, Nobumichi Fujimoto, Kiyohide Int J Mol Sci Article The clinical significance of regulatory T cells (Treg) and tumor-associated macrophages (TAM) in the tumor microenvironment of human bladder cancer remains unclear. The aim of this study is to explore their relevance to oncological features in non-muscle invasive bladder cancer (NMIBC). We carried out immunohistochemical analysis of forkhead box P3 (FOXP3, Treg maker), CD204 (TAM marker), and interleukin-6 (IL6) using surgical specimens obtained from 154 NMIBC patients. The Treg and TAM counts surrounding the cancer lesion and IL6-positive cancer cell counts were evaluated against clinicopathological variables. We focused on the ability of the Treg and TAM counts around the cancer lesion to predict outcomes after adjuvant intravesical Bacille Calmette–Guérin (BCG) treatment. High Treg counts were associated with female patients, older age, T1 category, and high tumor grade. TAM count was significantly correlated with Treg count and with IL6-positive cancer cell count. In our analysis of 71 patients treated with BCG, high counts of Treg and TAM were associated with shorter recurrence-free survival, and the former was an independent predictor of recurrence. Poor response to intravesical BCG was associated with Treg and TAM in the tumor microenvironment. Disrupting the immune network can be a supplementary therapeutic approach for NMIBC patients receiving intravesical BCG. MDPI 2017-10-19 /pmc/articles/PMC5666867/ /pubmed/29048388 http://dx.doi.org/10.3390/ijms18102186 Text en © 2017 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
Miyake, Makito
Tatsumi, Yoshihiro
Gotoh, Daisuke
Ohnishi, Sayuri
Owari, Takuya
Iida, Kota
Ohnishi, Kenta
Hori, Shunta
Morizawa, Yosuke
Itami, Yoshitaka
Nakai, Yasushi
Inoue, Takeshi
Anai, Satoshi
Torimoto, Kazumasa
Aoki, Katsuya
Shimada, Keiji
Konishi, Noboru
Tanaka, Nobumichi
Fujimoto, Kiyohide
Regulatory T Cells and Tumor-Associated Macrophages in the Tumor Microenvironment in Non-Muscle Invasive Bladder Cancer Treated with Intravesical Bacille Calmette-Guérin: A Long-Term Follow-Up Study of a Japanese Cohort
title Regulatory T Cells and Tumor-Associated Macrophages in the Tumor Microenvironment in Non-Muscle Invasive Bladder Cancer Treated with Intravesical Bacille Calmette-Guérin: A Long-Term Follow-Up Study of a Japanese Cohort
title_full Regulatory T Cells and Tumor-Associated Macrophages in the Tumor Microenvironment in Non-Muscle Invasive Bladder Cancer Treated with Intravesical Bacille Calmette-Guérin: A Long-Term Follow-Up Study of a Japanese Cohort
title_fullStr Regulatory T Cells and Tumor-Associated Macrophages in the Tumor Microenvironment in Non-Muscle Invasive Bladder Cancer Treated with Intravesical Bacille Calmette-Guérin: A Long-Term Follow-Up Study of a Japanese Cohort
title_full_unstemmed Regulatory T Cells and Tumor-Associated Macrophages in the Tumor Microenvironment in Non-Muscle Invasive Bladder Cancer Treated with Intravesical Bacille Calmette-Guérin: A Long-Term Follow-Up Study of a Japanese Cohort
title_short Regulatory T Cells and Tumor-Associated Macrophages in the Tumor Microenvironment in Non-Muscle Invasive Bladder Cancer Treated with Intravesical Bacille Calmette-Guérin: A Long-Term Follow-Up Study of a Japanese Cohort
title_sort regulatory t cells and tumor-associated macrophages in the tumor microenvironment in non-muscle invasive bladder cancer treated with intravesical bacille calmette-guérin: a long-term follow-up study of a japanese cohort
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666867/
https://www.ncbi.nlm.nih.gov/pubmed/29048388
http://dx.doi.org/10.3390/ijms18102186
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