IL6 modulates the immune status of the tumor microenvironment to facilitate metastatic colonization of colorectal cancer cells

Toyoshima, Yujiro; Kitamura, Hidemitsu; Xiang, Huihui; Ohno, Yosuke; Homma, Shigenori; Kawamura, Hideki; Takahashi, Norihiko; Kamiyama, Toshiya; Tanino, Mishie; Taketomi, Akinobu

IL6 modulates the immune status of the tumor microenvironment to facilitate metastatic colonization of colorectal cancer cells

Toyoshima, Yujiro; Kitamura, Hidemitsu; Xiang, Huihui et al.

Cancer Immunology Research, 2019, 7(12), 1944-1957

Permalink : https://hdl.handle.net/2115/79849

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論文情報

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アクセス権	open access
URI	https://hdl.handle.net/2115/79849
タイトル	IL6 modulates the immune status of the tumor microenvironment to facilitate metastatic colonization of colorectal cancer cells
著者	Toyoshima, Yujiro ; Kitamura, Hidemitsu ; Xiang, Huihui ; Ohno, Yosuke ; Homma, Shigenori ; Kawamura, Hideki ; Takahashi, Norihiko ; Kamiyama, Toshiya ; Tanino, Mishie ; Taketomi, Akinobu
著者名 Toyoshima, Yujiro
e-Rad_Researcher 40360531 著者名 Kitamura, Hidemitsu
著者名 Xiang, Huihui
著者名 Ohno, Yosuke
e-Rad_Researcher 30533674 著者名 Homma, Shigenori
e-Rad_Researcher 70645960 著者名 Kawamura, Hideki
e-Rad_Researcher 30399894 著者名 Takahashi, Norihiko
e-Rad_Researcher 80322816 著者名 Kamiyama, Toshiya
e-Rad_Researcher 90360908 著者名 Tanino, Mishie
e-Rad_Researcher 70363364 著者名 Taketomi, Akinobu
言語	英語
キーワード	IL6
	metastatic colonization
	colorectal cancer
	dendritic cells
	cytotoxic T cells
発行日	2019-12
出版者	American Association for Cancer Research (AACR)
収録物名	Cancer Immunology Research
巻(号)	7(12)
ページ	1944-1957
抄録	It is unknown as to how liver metastases are correlated with host immune status in colorectal cancer. In this study, we found that IL-6, a proinflammatory cytokine produced in tumor-bearing states, promotes the metastatic colonization of colon cancer cells in association with dysfunctional anti-tumor immunity. In IL-6-deficient mice, metastatic colonization of CT26 cells in the liver was reduced, and the anti-tumor effector function of CD8+ T cells as well as IL-12 production by CD11c+ dendritic cells were augmented in vivo. Furthermore, IL-6-deficient mice exhibited enhanced IFNAR1- mediated type I interferon signaling, which upregulated PD-L1 and MHC class I expression on CT26 cells. In vivo injection of anti-PD-L1 antibody effectively suppressed the metastatic colonization of CT26 cells in Il6-/- but not Il6+/+ mice. Finally, we confirmed that colorectal cancer patients with low IL-6 levels in their primary tumors showed prolonged disease-free survival. These findings suggest IL-6 may be a promising target for the treatment of metastasis in colorectal cancers by improving host immunity.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
PISSN	2326-6066
EISSN	2326-6074
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1158/2326-6066.CIR-18-0766