CD163+CD204+ tumor-associated macrophages contribute to T cell regulation via interleukin-10 and PD-L1 production in oral squamous cell carcinoma

Abstract Tumor-associated macrophages (TAMs) promote cancer cell proliferation, invasion, and metastasis by producing various mediators. Although preclinical studies demonstrated that TAMs preferentially express CD163 and CD204, the TAM subsets in oral squamous cell carcinoma (OSCC) remain unknown....

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Autores principales: Keigo Kubota, Masafumi Moriyama, Sachiko Furukawa, Haque A. S. M. Rafiul, Yasuyuki Maruse, Teppei Jinno, Akihiko Tanaka, Miho Ohta, Noriko Ishiguro, Masaaki Yamauchi, Mizuki Sakamoto, Takashi Maehara, Jun-Nosuke Hayashida, Shintaro Kawano, Tamotsu Kiyoshima, Seiji Nakamura
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:5eb629ab63b04451ae6df8ef9aa312e42021-12-02T16:06:09ZCD163+CD204+ tumor-associated macrophages contribute to T cell regulation via interleukin-10 and PD-L1 production in oral squamous cell carcinoma10.1038/s41598-017-01661-z2045-2322https://doaj.org/article/5eb629ab63b04451ae6df8ef9aa312e42017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01661-zhttps://doaj.org/toc/2045-2322Abstract Tumor-associated macrophages (TAMs) promote cancer cell proliferation, invasion, and metastasis by producing various mediators. Although preclinical studies demonstrated that TAMs preferentially express CD163 and CD204, the TAM subsets in oral squamous cell carcinoma (OSCC) remain unknown. In this study, we examined the expression and role of TAM subsets in OSCC. Forty-six patients with OSCC were analyzed for expression of TAMs in biopsy samples by immunohistochemistry. We examined TAM subsets and their production of immune suppressive molecules (IL-10 and PD-L1) in peripheral blood mononuclear cells from three OSCC patients by flow cytometry. CD163 was detected around the tumor or connective tissue, while CD204 was detected in/around the tumors. Flow cytometric analysis revealed that CD163+CD204+ TAMs strongly produced IL-10 and PD-L1 in comparison with CD163+CD204− and CD163−CD204+ TAMs. Furthermore, the number of activated CD3+ T cells after co-culture with CD163+CD204+ TAMs was significantly lower than that after co-culture with other TAM subsets. In clinical findings, the number of CD163+CD204+ TAMs was negatively correlated with that of CD25+ cells and 5-year progression-free survival. These results suggest that CD163+CD204+ TAMs possibly play a key role in the invasion and metastasis of OSCC by T-cell regulation via IL-10 and PD-L1 production.Keigo KubotaMasafumi MoriyamaSachiko FurukawaHaque A. S. M. RafiulYasuyuki MaruseTeppei JinnoAkihiko TanakaMiho OhtaNoriko IshiguroMasaaki YamauchiMizuki SakamotoTakashi MaeharaJun-Nosuke HayashidaShintaro KawanoTamotsu KiyoshimaSeiji NakamuraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Keigo Kubota
Masafumi Moriyama
Sachiko Furukawa
Haque A. S. M. Rafiul
Yasuyuki Maruse
Teppei Jinno
Akihiko Tanaka
Miho Ohta
Noriko Ishiguro
Masaaki Yamauchi
Mizuki Sakamoto
Takashi Maehara
Jun-Nosuke Hayashida
Shintaro Kawano
Tamotsu Kiyoshima
Seiji Nakamura
CD163+CD204+ tumor-associated macrophages contribute to T cell regulation via interleukin-10 and PD-L1 production in oral squamous cell carcinoma
description Abstract Tumor-associated macrophages (TAMs) promote cancer cell proliferation, invasion, and metastasis by producing various mediators. Although preclinical studies demonstrated that TAMs preferentially express CD163 and CD204, the TAM subsets in oral squamous cell carcinoma (OSCC) remain unknown. In this study, we examined the expression and role of TAM subsets in OSCC. Forty-six patients with OSCC were analyzed for expression of TAMs in biopsy samples by immunohistochemistry. We examined TAM subsets and their production of immune suppressive molecules (IL-10 and PD-L1) in peripheral blood mononuclear cells from three OSCC patients by flow cytometry. CD163 was detected around the tumor or connective tissue, while CD204 was detected in/around the tumors. Flow cytometric analysis revealed that CD163+CD204+ TAMs strongly produced IL-10 and PD-L1 in comparison with CD163+CD204− and CD163−CD204+ TAMs. Furthermore, the number of activated CD3+ T cells after co-culture with CD163+CD204+ TAMs was significantly lower than that after co-culture with other TAM subsets. In clinical findings, the number of CD163+CD204+ TAMs was negatively correlated with that of CD25+ cells and 5-year progression-free survival. These results suggest that CD163+CD204+ TAMs possibly play a key role in the invasion and metastasis of OSCC by T-cell regulation via IL-10 and PD-L1 production.
format article
author Keigo Kubota
Masafumi Moriyama
Sachiko Furukawa
Haque A. S. M. Rafiul
Yasuyuki Maruse
Teppei Jinno
Akihiko Tanaka
Miho Ohta
Noriko Ishiguro
Masaaki Yamauchi
Mizuki Sakamoto
Takashi Maehara
Jun-Nosuke Hayashida
Shintaro Kawano
Tamotsu Kiyoshima
Seiji Nakamura
author_facet Keigo Kubota
Masafumi Moriyama
Sachiko Furukawa
Haque A. S. M. Rafiul
Yasuyuki Maruse
Teppei Jinno
Akihiko Tanaka
Miho Ohta
Noriko Ishiguro
Masaaki Yamauchi
Mizuki Sakamoto
Takashi Maehara
Jun-Nosuke Hayashida
Shintaro Kawano
Tamotsu Kiyoshima
Seiji Nakamura
author_sort Keigo Kubota
title CD163+CD204+ tumor-associated macrophages contribute to T cell regulation via interleukin-10 and PD-L1 production in oral squamous cell carcinoma
title_short CD163+CD204+ tumor-associated macrophages contribute to T cell regulation via interleukin-10 and PD-L1 production in oral squamous cell carcinoma
title_full CD163+CD204+ tumor-associated macrophages contribute to T cell regulation via interleukin-10 and PD-L1 production in oral squamous cell carcinoma
title_fullStr CD163+CD204+ tumor-associated macrophages contribute to T cell regulation via interleukin-10 and PD-L1 production in oral squamous cell carcinoma
title_full_unstemmed CD163+CD204+ tumor-associated macrophages contribute to T cell regulation via interleukin-10 and PD-L1 production in oral squamous cell carcinoma
title_sort cd163+cd204+ tumor-associated macrophages contribute to t cell regulation via interleukin-10 and pd-l1 production in oral squamous cell carcinoma
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/5eb629ab63b04451ae6df8ef9aa312e4
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