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Intraperitoneal neutrophils activated by KRAS-induced ovarian cancer exert antitumor effects by modulating adaptive immunity

Increased neutrophil counts are a hallmark of a poor prognosis for cancer. We previously reported that KRAS promoted tumorigenesis and increased neutrophil counts in a mouse peritoneal cancer model. In the current study, we evaluated the role of increased neutrophils in cancer progression, as well a...

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Autores principales: Yoshida, Mitsuyo, Taguchi, Ayumi, Kawana, Kei, Ogishima, Juri, Adachi, Katsuyuki, Kawata, Akira, Nakamura, Hiroe, Sato, Masakazu, Fujimoto, Asaha, Inoue, Tomoko, Tomio, Kensuke, Mori, Mayuyo, Nagamatsu, Takeshi, Arimoto, Takahide, Koga, Kaori, Hiraike, Osamu Wada, Oda, Katsutoshi, Kiyono, Tohru, Osuga, Yutaka, Fujii, Tomoyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086631/
https://www.ncbi.nlm.nih.gov/pubmed/30066851
http://dx.doi.org/10.3892/ijo.2018.4504
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author Yoshida, Mitsuyo
Taguchi, Ayumi
Kawana, Kei
Ogishima, Juri
Adachi, Katsuyuki
Kawata, Akira
Nakamura, Hiroe
Sato, Masakazu
Fujimoto, Asaha
Inoue, Tomoko
Tomio, Kensuke
Mori, Mayuyo
Nagamatsu, Takeshi
Arimoto, Takahide
Koga, Kaori
Hiraike, Osamu Wada
Oda, Katsutoshi
Kiyono, Tohru
Osuga, Yutaka
Fujii, Tomoyuki
author_facet Yoshida, Mitsuyo
Taguchi, Ayumi
Kawana, Kei
Ogishima, Juri
Adachi, Katsuyuki
Kawata, Akira
Nakamura, Hiroe
Sato, Masakazu
Fujimoto, Asaha
Inoue, Tomoko
Tomio, Kensuke
Mori, Mayuyo
Nagamatsu, Takeshi
Arimoto, Takahide
Koga, Kaori
Hiraike, Osamu Wada
Oda, Katsutoshi
Kiyono, Tohru
Osuga, Yutaka
Fujii, Tomoyuki
author_sort Yoshida, Mitsuyo
collection PubMed
description Increased neutrophil counts are a hallmark of a poor prognosis for cancer. We previously reported that KRAS promoted tumorigenesis and increased neutrophil counts in a mouse peritoneal cancer model. In the current study, we evaluated the role of increased neutrophils in cancer progression, as well as their influence on the intraperitoneal microenvironment. A mouse peritoneal cancer model was established using the KRAS-transduced mouse ovarian cancer cell line, ID8-KRAS. Neutrophil function was assessed by neutrophil depletion in ID8-KRAS mice. Neutrophil depletion markedly accelerated tumor formation; this was accompanied by an increase in interleukin-6 concentrations in ascites. Neutrophil depletion significantly decreased the amount of local and systemic CD8(+) T cells, while increasing the amount of local CD4(+) T cells, accompanied by an increased amount of monocytic myeloid-derived suppressor cells (M-MDSCs) and regulatory T cells (Tregs) (P<0.05). The roles of peritoneal neutrophils (PENs) in CD8(+) T cell activation were assessed in vitro. PENs of ID8-KRAS mice had a strong potential to enhance T cell proliferation with a higher expression of the T cell costimulatory molecules OX40 ligand (OX40L) and 4-1BB ligand (4-1BBL), as compared with peripheral blood neutrophils (PBNs). These findings suggest that neutrophils recruited into the KRAS-induced tumor microenvironment (TME) have antitumor properties with the potential to modulate the numbers of M-MDSCs and Tregs and activate CD8(+) T cells through T cell costimulatory molecules.
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spelling pubmed-60866312018-08-13 Intraperitoneal neutrophils activated by KRAS-induced ovarian cancer exert antitumor effects by modulating adaptive immunity Yoshida, Mitsuyo Taguchi, Ayumi Kawana, Kei Ogishima, Juri Adachi, Katsuyuki Kawata, Akira Nakamura, Hiroe Sato, Masakazu Fujimoto, Asaha Inoue, Tomoko Tomio, Kensuke Mori, Mayuyo Nagamatsu, Takeshi Arimoto, Takahide Koga, Kaori Hiraike, Osamu Wada Oda, Katsutoshi Kiyono, Tohru Osuga, Yutaka Fujii, Tomoyuki Int J Oncol Articles Increased neutrophil counts are a hallmark of a poor prognosis for cancer. We previously reported that KRAS promoted tumorigenesis and increased neutrophil counts in a mouse peritoneal cancer model. In the current study, we evaluated the role of increased neutrophils in cancer progression, as well as their influence on the intraperitoneal microenvironment. A mouse peritoneal cancer model was established using the KRAS-transduced mouse ovarian cancer cell line, ID8-KRAS. Neutrophil function was assessed by neutrophil depletion in ID8-KRAS mice. Neutrophil depletion markedly accelerated tumor formation; this was accompanied by an increase in interleukin-6 concentrations in ascites. Neutrophil depletion significantly decreased the amount of local and systemic CD8(+) T cells, while increasing the amount of local CD4(+) T cells, accompanied by an increased amount of monocytic myeloid-derived suppressor cells (M-MDSCs) and regulatory T cells (Tregs) (P<0.05). The roles of peritoneal neutrophils (PENs) in CD8(+) T cell activation were assessed in vitro. PENs of ID8-KRAS mice had a strong potential to enhance T cell proliferation with a higher expression of the T cell costimulatory molecules OX40 ligand (OX40L) and 4-1BB ligand (4-1BBL), as compared with peripheral blood neutrophils (PBNs). These findings suggest that neutrophils recruited into the KRAS-induced tumor microenvironment (TME) have antitumor properties with the potential to modulate the numbers of M-MDSCs and Tregs and activate CD8(+) T cells through T cell costimulatory molecules. D.A. Spandidos 2018-07-26 /pmc/articles/PMC6086631/ /pubmed/30066851 http://dx.doi.org/10.3892/ijo.2018.4504 Text en Copyright: © Yoshida et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , 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 Articles
Yoshida, Mitsuyo
Taguchi, Ayumi
Kawana, Kei
Ogishima, Juri
Adachi, Katsuyuki
Kawata, Akira
Nakamura, Hiroe
Sato, Masakazu
Fujimoto, Asaha
Inoue, Tomoko
Tomio, Kensuke
Mori, Mayuyo
Nagamatsu, Takeshi
Arimoto, Takahide
Koga, Kaori
Hiraike, Osamu Wada
Oda, Katsutoshi
Kiyono, Tohru
Osuga, Yutaka
Fujii, Tomoyuki
Intraperitoneal neutrophils activated by KRAS-induced ovarian cancer exert antitumor effects by modulating adaptive immunity
title Intraperitoneal neutrophils activated by KRAS-induced ovarian cancer exert antitumor effects by modulating adaptive immunity
title_full Intraperitoneal neutrophils activated by KRAS-induced ovarian cancer exert antitumor effects by modulating adaptive immunity
title_fullStr Intraperitoneal neutrophils activated by KRAS-induced ovarian cancer exert antitumor effects by modulating adaptive immunity
title_full_unstemmed Intraperitoneal neutrophils activated by KRAS-induced ovarian cancer exert antitumor effects by modulating adaptive immunity
title_short Intraperitoneal neutrophils activated by KRAS-induced ovarian cancer exert antitumor effects by modulating adaptive immunity
title_sort intraperitoneal neutrophils activated by kras-induced ovarian cancer exert antitumor effects by modulating adaptive immunity
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086631/
https://www.ncbi.nlm.nih.gov/pubmed/30066851
http://dx.doi.org/10.3892/ijo.2018.4504
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