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Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma
BACKGROUND: Inflammation and immune characteristics of the tumour microenvironment have therapeutic significance. The aim of this study was to investigate the clinical impact on disease progression in human extrahepatic cholangiocarcinoma (ECC). METHODS: A total of 114 consecutive ECC patients with...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785749/ https://www.ncbi.nlm.nih.gov/pubmed/29123259 http://dx.doi.org/10.1038/bjc.2017.401 |
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author | Kitano, Yuki Okabe, Hirohisa Yamashita, Yo-ichi Nakagawa, Shigeki Saito, Yoichi Umezaki, Naoki Tsukamoto, Masayo Yamao, Takanobu Yamamura, Kensuke Arima, Kota Kaida, Takayoshi Miyata, Tatsunori Mima, Kosuke Imai, Katsunori Hashimoto, Daisuke Komohara, Yoshihiro Chikamoto, Akira Ishiko, Takatoshi Baba, Hideo |
author_facet | Kitano, Yuki Okabe, Hirohisa Yamashita, Yo-ichi Nakagawa, Shigeki Saito, Yoichi Umezaki, Naoki Tsukamoto, Masayo Yamao, Takanobu Yamamura, Kensuke Arima, Kota Kaida, Takayoshi Miyata, Tatsunori Mima, Kosuke Imai, Katsunori Hashimoto, Daisuke Komohara, Yoshihiro Chikamoto, Akira Ishiko, Takatoshi Baba, Hideo |
author_sort | Kitano, Yuki |
collection | PubMed |
description | BACKGROUND: Inflammation and immune characteristics of the tumour microenvironment have therapeutic significance. The aim of this study was to investigate the clinical impact on disease progression in human extrahepatic cholangiocarcinoma (ECC). METHODS: A total of 114 consecutive ECC patients with curative resection between 2000 and 2014 were enrolled. Tumour infiltrating CD66b(+) neutrophils (TANs; tumour associated neutrophils), CD163(+) M2 macrophages (TAMs; tumour associated macrophages), CD8(+) T cells, and FOXP3(+) regulatory T cells (Tregs) were assayed by immunohistochemistry, and their relationships with patient clinicopathological characteristics and prognosis were evaluated. RESULTS: Tumour associated neutrophils were inversely correlated with CD8(+) T cells (P=0.0001) and positively correlated with Tregs (P=0.001). High TANs (P=0.01), low CD8(+) T cells (P=0.02), and high Tregs (P=0.04) were significantly associated with poor overall survival (OS). A high-risk signature, derived from integration of intratumoural inflammatory and immune cells, was significantly associated with poor recurrence-free survival (P=0.01) and OS (P=0.0008). A high-risk signature was correlated with postoperative distant metastases. Furthermore, a high-risk signature was related to the resistance to gemcitabine-based chemotherapy used after recurrence. CONCLUSIONS: Our data showed that tumour infiltrating inflammatory and immune cells may play a pivotal role in ECC progression and a high-risk signature predicted poor prognosis in ECC patients. |
format | Online Article Text |
id | pubmed-5785749 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-57857492019-01-01 Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma Kitano, Yuki Okabe, Hirohisa Yamashita, Yo-ichi Nakagawa, Shigeki Saito, Yoichi Umezaki, Naoki Tsukamoto, Masayo Yamao, Takanobu Yamamura, Kensuke Arima, Kota Kaida, Takayoshi Miyata, Tatsunori Mima, Kosuke Imai, Katsunori Hashimoto, Daisuke Komohara, Yoshihiro Chikamoto, Akira Ishiko, Takatoshi Baba, Hideo Br J Cancer Clinical Study BACKGROUND: Inflammation and immune characteristics of the tumour microenvironment have therapeutic significance. The aim of this study was to investigate the clinical impact on disease progression in human extrahepatic cholangiocarcinoma (ECC). METHODS: A total of 114 consecutive ECC patients with curative resection between 2000 and 2014 were enrolled. Tumour infiltrating CD66b(+) neutrophils (TANs; tumour associated neutrophils), CD163(+) M2 macrophages (TAMs; tumour associated macrophages), CD8(+) T cells, and FOXP3(+) regulatory T cells (Tregs) were assayed by immunohistochemistry, and their relationships with patient clinicopathological characteristics and prognosis were evaluated. RESULTS: Tumour associated neutrophils were inversely correlated with CD8(+) T cells (P=0.0001) and positively correlated with Tregs (P=0.001). High TANs (P=0.01), low CD8(+) T cells (P=0.02), and high Tregs (P=0.04) were significantly associated with poor overall survival (OS). A high-risk signature, derived from integration of intratumoural inflammatory and immune cells, was significantly associated with poor recurrence-free survival (P=0.01) and OS (P=0.0008). A high-risk signature was correlated with postoperative distant metastases. Furthermore, a high-risk signature was related to the resistance to gemcitabine-based chemotherapy used after recurrence. CONCLUSIONS: Our data showed that tumour infiltrating inflammatory and immune cells may play a pivotal role in ECC progression and a high-risk signature predicted poor prognosis in ECC patients. Nature Publishing Group 2018-01 2017-11-09 /pmc/articles/PMC5785749/ /pubmed/29123259 http://dx.doi.org/10.1038/bjc.2017.401 Text en Copyright © 2018 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/4.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
spellingShingle | Clinical Study Kitano, Yuki Okabe, Hirohisa Yamashita, Yo-ichi Nakagawa, Shigeki Saito, Yoichi Umezaki, Naoki Tsukamoto, Masayo Yamao, Takanobu Yamamura, Kensuke Arima, Kota Kaida, Takayoshi Miyata, Tatsunori Mima, Kosuke Imai, Katsunori Hashimoto, Daisuke Komohara, Yoshihiro Chikamoto, Akira Ishiko, Takatoshi Baba, Hideo Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma |
title | Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma |
title_full | Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma |
title_fullStr | Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma |
title_full_unstemmed | Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma |
title_short | Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma |
title_sort | tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma |
topic | Clinical Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5785749/ https://www.ncbi.nlm.nih.gov/pubmed/29123259 http://dx.doi.org/10.1038/bjc.2017.401 |
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