| Title: | Lack of interleukin-6 in the tumor microenvironment augments type-1 immunity and increases the efficacy of cancer immunotherapy |
| Authors: | Ohno, Yosuke Browse this author |
| Toyoshima, Yujiro Browse this author |
| Yurino, Hideaki Browse this author |
| Monma, Norikazu Browse this author |
| Xiang, Huihui Browse this author |
| Sumida, Kentaro Browse this author |
| Kaneumi, Shun Browse this author |
| Terada, Satoshi Browse this author |
| Hashimoto, Shinichi Browse this author |
| Ikeo, Kazuho Browse this author |
| Homma, Shigenori Browse this author →KAKEN DB |
| Kawamura, Hideki Browse this author →KAKEN DB |
| Takahashi, Norihiko Browse this author |
| Taketomi, Akinobu Browse this author →KAKEN DB |
| Kitamura, Hidemitsu Browse this author →KAKEN DB |
| Keywords: | Cytotoxic T cells |
| dendritic cells |
| interferon-γ |
| interleukin-6 |
| programmed death-ligand 1 |
| Issue Date: | Oct-2017 |
| Publisher: | John Wiley & Sons |
| Journal Title: | Cancer science |
| Volume: | 108 |
| Issue: | 10 |
| Start Page: | 1959 |
| End Page: | 1966 |
| Publisher DOI: | 10.1111/cas.13330 |
| Abstract: | 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. |
| Rights: | http://creativecommons.org/licenses/by-nc/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/67656 |
| 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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