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PD‐L1 expression enhancement by infiltrating macrophage‐derived tumor necrosis factor‐α leads to poor pancreatic cancer prognosis

Immunotherapy using anti‐PD‐1/PD‐L1 antibodies for several types of cancer has received considerable attention in recent decades. However, the molecular mechanism underlying PD‐L1 expression in pancreatic ductal adenocarcinoma (PDAC) cells has not been clearly elucidated. We investigated the clinica...

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Autores principales: Tsukamoto, Masayo, Imai, Katsunori, Ishimoto, Takatsugu, Komohara, Yoshihiro, Yamashita, Yo‐ichi, Nakagawa, Shigeki, Umezaki, Naoki, Yamao, Takanobu, Kitano, Yuki, Miyata, Tatsunori, Arima, Kota, Okabe, Hirohisa, Baba, Yoshifumi, Chikamoto, Akira, Ishiko, Takatoshi, Hirota, Masahiko, Baba, Hideo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317925/
https://www.ncbi.nlm.nih.gov/pubmed/30426611
http://dx.doi.org/10.1111/cas.13874
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author Tsukamoto, Masayo
Imai, Katsunori
Ishimoto, Takatsugu
Komohara, Yoshihiro
Yamashita, Yo‐ichi
Nakagawa, Shigeki
Umezaki, Naoki
Yamao, Takanobu
Kitano, Yuki
Miyata, Tatsunori
Arima, Kota
Okabe, Hirohisa
Baba, Yoshifumi
Chikamoto, Akira
Ishiko, Takatoshi
Hirota, Masahiko
Baba, Hideo
author_facet Tsukamoto, Masayo
Imai, Katsunori
Ishimoto, Takatsugu
Komohara, Yoshihiro
Yamashita, Yo‐ichi
Nakagawa, Shigeki
Umezaki, Naoki
Yamao, Takanobu
Kitano, Yuki
Miyata, Tatsunori
Arima, Kota
Okabe, Hirohisa
Baba, Yoshifumi
Chikamoto, Akira
Ishiko, Takatoshi
Hirota, Masahiko
Baba, Hideo
author_sort Tsukamoto, Masayo
collection PubMed
description Immunotherapy using anti‐PD‐1/PD‐L1 antibodies for several types of cancer has received considerable attention in recent decades. However, the molecular mechanism underlying PD‐L1 expression in pancreatic ductal adenocarcinoma (PDAC) cells has not been clearly elucidated. We investigated the clinical significance and regulatory mechanism of PD‐L1 expression in PDAC cells. Among the various cytokines tested, tumor necrosis factor (TNF)‐α upregulated PD‐L1 expression in PDAC cells through NF‐κB signaling. The induction of PD‐L1 expression was also caused by co‐culture with activated macrophages, and the upregulation was inhibited by neutralization with anti‐TNF‐α antibody after co‐culture with activated macrophages. PD‐L1 expression in PDAC cells was positively correlated with macrophage infiltration in tumor stroma of human PDAC tissues. In addition, survival analysis revealed that high PD‐L1 expression was significantly associated with poor prognosis in 235 PDAC patients and especially in patients harboring high CD8‐positive T‐cell infiltration. These findings indicate that tumor‐infiltrating macrophage‐derived TNF‐α could be a potential therapeutic target for PDAC.
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spelling pubmed-63179252019-01-08 PD‐L1 expression enhancement by infiltrating macrophage‐derived tumor necrosis factor‐α leads to poor pancreatic cancer prognosis Tsukamoto, Masayo Imai, Katsunori Ishimoto, Takatsugu Komohara, Yoshihiro Yamashita, Yo‐ichi Nakagawa, Shigeki Umezaki, Naoki Yamao, Takanobu Kitano, Yuki Miyata, Tatsunori Arima, Kota Okabe, Hirohisa Baba, Yoshifumi Chikamoto, Akira Ishiko, Takatoshi Hirota, Masahiko Baba, Hideo Cancer Sci Original Articles Immunotherapy using anti‐PD‐1/PD‐L1 antibodies for several types of cancer has received considerable attention in recent decades. However, the molecular mechanism underlying PD‐L1 expression in pancreatic ductal adenocarcinoma (PDAC) cells has not been clearly elucidated. We investigated the clinical significance and regulatory mechanism of PD‐L1 expression in PDAC cells. Among the various cytokines tested, tumor necrosis factor (TNF)‐α upregulated PD‐L1 expression in PDAC cells through NF‐κB signaling. The induction of PD‐L1 expression was also caused by co‐culture with activated macrophages, and the upregulation was inhibited by neutralization with anti‐TNF‐α antibody after co‐culture with activated macrophages. PD‐L1 expression in PDAC cells was positively correlated with macrophage infiltration in tumor stroma of human PDAC tissues. In addition, survival analysis revealed that high PD‐L1 expression was significantly associated with poor prognosis in 235 PDAC patients and especially in patients harboring high CD8‐positive T‐cell infiltration. These findings indicate that tumor‐infiltrating macrophage‐derived TNF‐α could be a potential therapeutic target for PDAC. John Wiley and Sons Inc. 2018-12-14 2019-01 /pmc/articles/PMC6317925/ /pubmed/30426611 http://dx.doi.org/10.1111/cas.13874 Text en © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Tsukamoto, Masayo
Imai, Katsunori
Ishimoto, Takatsugu
Komohara, Yoshihiro
Yamashita, Yo‐ichi
Nakagawa, Shigeki
Umezaki, Naoki
Yamao, Takanobu
Kitano, Yuki
Miyata, Tatsunori
Arima, Kota
Okabe, Hirohisa
Baba, Yoshifumi
Chikamoto, Akira
Ishiko, Takatoshi
Hirota, Masahiko
Baba, Hideo
PD‐L1 expression enhancement by infiltrating macrophage‐derived tumor necrosis factor‐α leads to poor pancreatic cancer prognosis
title PD‐L1 expression enhancement by infiltrating macrophage‐derived tumor necrosis factor‐α leads to poor pancreatic cancer prognosis
title_full PD‐L1 expression enhancement by infiltrating macrophage‐derived tumor necrosis factor‐α leads to poor pancreatic cancer prognosis
title_fullStr PD‐L1 expression enhancement by infiltrating macrophage‐derived tumor necrosis factor‐α leads to poor pancreatic cancer prognosis
title_full_unstemmed PD‐L1 expression enhancement by infiltrating macrophage‐derived tumor necrosis factor‐α leads to poor pancreatic cancer prognosis
title_short PD‐L1 expression enhancement by infiltrating macrophage‐derived tumor necrosis factor‐α leads to poor pancreatic cancer prognosis
title_sort pd‐l1 expression enhancement by infiltrating macrophage‐derived tumor necrosis factor‐α leads to poor pancreatic cancer prognosis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6317925/
https://www.ncbi.nlm.nih.gov/pubmed/30426611
http://dx.doi.org/10.1111/cas.13874
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