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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Medicine / Faculty of Medicine >
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Vaccine immunotherapy with ARNAX induces tumor-specific memory T cells and durable anti-tumor immunity in mouse models
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| Title: | Vaccine immunotherapy with ARNAX induces tumor-specific memory T cells and durable anti-tumor immunity in mouse models |
| Authors: | Takeda, Yohei Browse this author | | Yoshida, Sumito Browse this author | | Takashima, Ken Browse this author | | Ishii-Mugikura, Noriko Browse this author | | Shime, Hiroaki Browse this author →KAKEN DB | | Seya, Tsukasa Browse this author →KAKEN DB | | Matsumoto, Misako Browse this author →KAKEN DB |
| Keywords: | cancer immunotherapy | | memory CD8+ T cell | | PD-L1 blockade | | Toll-like receptor 3 adjuvant | | tumor microenvironment |
| Issue Date: | Jul-2018 |
| Publisher: | John Wiley & Sons |
| Journal Title: | Cancer science |
| Volume: | 109 |
| Issue: | 7 |
| Start Page: | 2119 |
| End Page: | 2129 |
| Publisher DOI: | 10.1111/cas.13649 |
| Abstract: | Immunological checkpoint blockade therapies benefit a limited population of cancer patients. We have previously shown that vaccine immunotherapy with Toll-like receptor (TLR)3-adjuvant and tumor antigen overcomes anti-programmed death ligand-1 (PD-L1) resistance in mouse tumor models. In the present study, 4 different ovalbumin (OVA)-expressing tumor cell lines were implanted into syngeneic mice and subjected to anti-tumor immunotherapy using ARNAX and whole OVA protein. ARNAX is a TLR3-specific agonist that does not activate the mitochondrial antiviral-signaling protein (MAVS) pathway, and thus does not induce systemic inflammation. Dendritic cell priming and proliferative CTL were induced by ARNAX + OVA, but complete remission was achieved only in a PD-L1-low cell line of EG7. Addition of anti-PD-L1 antibody to the ARNAX + OVA therapy brought complete remission to another PD-L1-high subline of EG7. Tumor shrinkage but not remission was observed in MO5 in that regimen. We analyzed tumor cells and tumor-infiltrating immune cells to identify factors associated with successful ARNAX vaccine therapy. Tumors that responded to ARNAX therapy expressed high levels of MHC class I and low levels of PD-L1. The tumor-infiltrating immune cells in ARNAX-susceptible tumors contained fewer immunosuppressive myeloid cells with low PD-L1 expression. Combination with anti-PD-L1 antibody functioned not only within tumor sites but also within lymphoid tissues, augmenting the therapeutic efficacy of the ARNAX vaccine. Notably, ARNAX therapy induced memory CD8+ T cells and rejection of reimplanted tumors. Thus, ARNAX vaccine + anti-PD-L1 therapy enabled permanent remission against some tumors that stably present antigens. |
| Rights: | http://creativecommons.org/licenses/by-nc/4.0/ |
| Type: | article |
| URI: | http://hdl.handle.net/2115/71370 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 松本 美佐子
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