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IL6 modulates the immune status of the tumor microenvironment to facilitate metastatic colonization of colorectal cancer cells
Title: | IL6 modulates the immune status of the tumor microenvironment to facilitate metastatic colonization of colorectal cancer cells |
Authors: | Toyoshima, Yujiro Browse this author | Kitamura, Hidemitsu Browse this author →KAKEN DB | Xiang, Huihui Browse this author | Ohno, Yosuke Browse this author | Homma, Shigenori Browse this author →KAKEN DB | Kawamura, Hideki Browse this author →KAKEN DB | Takahashi, Norihiko Browse this author →KAKEN DB | Kamiyama, Toshiya Browse this author →KAKEN DB | Tanino, Mishie Browse this author →KAKEN DB | Taketomi, Akinobu Browse this author →KAKEN DB |
Keywords: | IL6 | metastatic colonization | colorectal cancer | dendritic cells | cytotoxic T cells |
Issue Date: | Dec-2019 |
Publisher: | American Association for Cancer Research (AACR) |
Journal Title: | Cancer Immunology Research |
Volume: | 7 |
Issue: | 12 |
Start Page: | 1944 |
End Page: | 1957 |
Publisher DOI: | 10.1158/2326-6066.CIR-18-0766 |
Abstract: | 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. |
Type: | article (author version) |
URI: | http://hdl.handle.net/2115/79849 |
Appears in Collections: | 遺伝子病制御研究所 (Institute for Genetic Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 北村 秀光
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