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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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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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. |
format | Online Article Text |
id | pubmed-5666867 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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