Lack of interleukin-6 in the tumor microenvironment augments type-1 immunity and increases the efficacy of cancer immunotherapy

Ohno, Yosuke; Toyoshima, Yujiro; Yurino, Hideaki; Monma, Norikazu; Xiang, Huihui; Sumida, Kentaro; Kaneumi, Shun; Terada, Satoshi; Hashimoto, Shinichi; Ikeo, Kazuho; Homma, Shigenori; Kawamura, Hideki; Takahashi, Norihiko; Taketomi, Akinobu; Kitamura, Hidemitsu

Lack of interleukin-6 in the tumor microenvironment augments type-1 immunity and increases the efficacy of cancer immunotherapy

Ohno, Yosuke; Toyoshima, Yujiro; Yurino, Hideaki et al.

Cancer science, 2017, 108(10), 1959-1966

Permalink : https://hdl.handle.net/2115/67656

このアイテムのアクセス数:1,067件（2026-08-17 04:55 集計）

閲覧可能ファイル

ファイル	フォーマット	サイズ	閲覧回数	説明
Ohno_et_al-2017-Cancer_Science	pdf	1.20 MB	638
cas13330-sup-0001-FigS1	tiff	3.63 MB	330	Supporting Information: Fig. S1
cas13330-sup-0002-FigS2	tiff	3.63 MB	335	Supporting Information: Fig. S2
cas13330-sup-0003-FigS3	tiff	3.63 MB	348	Supporting Information: Fig. S3
cas13330-sup-0004-FigS4	tiff	3.63 MB	336	Supporting Information: Fig. S4
cas13330-sup-0005-FigS5	tiff	3.63 MB	354	Supporting Information: Fig. S5

論文情報

ファイル出力 EndNote Basic出力 Mendeley出力

アクセス権	open access
URI	https://hdl.handle.net/2115/67656
タイトル	Lack of interleukin-6 in the tumor microenvironment augments type-1 immunity and increases the efficacy of cancer immunotherapy
著者	Ohno, Yosuke ; Toyoshima, Yujiro ; Yurino, Hideaki ; Monma, Norikazu ; Xiang, Huihui ; Sumida, Kentaro ; Kaneumi, Shun ; Terada, Satoshi ; Hashimoto, Shinichi ; Ikeo, Kazuho ; Homma, Shigenori ; Kawamura, Hideki ; Takahashi, Norihiko ; Taketomi, Akinobu ; Kitamura, Hidemitsu
著者名 Ohno, Yosuke
著者名 Toyoshima, Yujiro
著者名 Yurino, Hideaki
著者名 Monma, Norikazu
著者名 Xiang, Huihui
著者名 Sumida, Kentaro
著者名 Kaneumi, Shun
著者名 Terada, Satoshi
著者名 Hashimoto, Shinichi
著者名 Ikeo, Kazuho
e-Rad_Researcher 30533674 著者名 Homma, Shigenori
e-Rad_Researcher 70645960 著者名 Kawamura, Hideki
著者名 Takahashi, Norihiko
e-Rad_Researcher 70363364 著者名 Taketomi, Akinobu
e-Rad_Researcher 40360531 著者名 Kitamura, Hidemitsu
言語	英語
キーワード	Cytotoxic T cells
	dendritic cells
	interferon-γ
	interleukin-6
	programmed death-ligand 1
発行日	2017-10
出版者	John Wiley & Sons
収録物名	Cancer science
巻(号)	108(10)
ページ	1959-1966
抄録	Conquering immunosuppression in tumor microenvironments is crucial for effective cancer immunotherapy. It is well known that interleukin (IL)-6, a pleiotropic cytokine, is produced in the tumor-bearing state. In the present study, we investigated the precise effects of IL-6 on antitumor immunity and the subsequent tumorigenesis in tumor-bearing hosts. CT26 cells, a murine colon cancer cell line, were intradermally injected into wild-type and IL-6-deficient mice. As a result, we found that tumor growth was decreased significantly in IL-6-deficient mice compared with wild-type mice and the reduction was abrogated by depletion of CD8+ T cells. We further evaluated the immune status of tumor microenvironments and confirmed that mature dendritic cells, helper T cells and cytotoxic T cells were highly accumulated in tumor sites under the IL-6-deficient condition. In addition, higher numbers of interferon (IFN)-γ-producing T cells were present in the tumor tissues of IL-6-deficient mice compared with wild-type mice. Surface expression levels of programmed death-ligand 1 (PD-L1) and MHC class I on CT26 cells were enhanced under the IL-6-deficient condition in vivo and by IFN-γ stimulation in vitro. Finally, we confirmed that in vivo injection of an anti-PD-L1 antibody or a Toll-like receptor 3 ligand, polyinosinic-polycytidylic acid, effectively inhibited tumorigenesis under the IL-6-deficient condition. Based on these findings, we speculate that a lack of IL-6 produced in tumor-bearing host augments induction of antitumor effector T cells and inhibits tumorigenesis in vivo, suggesting that IL-6 signaling may be a promising target for the development of effective cancer immunotherapies.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution-NonCommercial 4.0 International
PISSN	1349-7006
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1111/cas.13330