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Antigen delivery targeted to tumor-associated macrophages overcomes tumor immune resistance
http://hdl.handle.net/10069/38899
http://hdl.handle.net/10069/388999d1cf511-bb31-4f2e-8284-d7f37da7f46c
名前 / ファイル | ライセンス | アクション |
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JCI129_1278.pdf (7.3 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2019-03-26 | |||||
タイトル | ||||||
タイトル | Antigen delivery targeted to tumor-associated macrophages overcomes tumor immune resistance | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Cancer immunotherapy | |||||
キーワード | ||||||
主題Scheme | Other | |||||
主題 | Immunology | |||||
資源タイプ | ||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
資源タイプ | journal article | |||||
著者 |
Muraoka, Daisuke
× Muraoka, Daisuke× Seo, Naohiro× Hayashi, Tae× Tahara, Yoshiro× Fujii, Keisuke× Tawara, Isao× Miyahara, Yoshihiro× Okamori, Kana× Yagita, Hideo× Imoto, Seiya× Yamaguchi, Rui× Komura, Mitsuhiro× Miyano, Satoru× Goto, Masahiro× Sawada, Shin-ichi× Asai, Akira× Ikeda, Hiroaki× Akiyoshi, Kazunari× Harada, Naozumi× Shiku, Hiroshi |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Immune checkpoint inhibitors and adoptive transfer of gene-engineered T cells have emerged as novel therapeutic modalities for hard-to-treat solid tumors; however, many patients are refractory to these immunotherapies, and the mechanisms underlying tumor immune resistance have not been fully elucidated. By comparing the tumor microenvironment of checkpoint inhibition-sensitive and -resistant murine solid tumors, we observed that the resistant tumors had low immunogenicity. We identified antigen presentation by CD11b+F4/80+ tumor-associated macrophages (TAMs) as a key factor correlated with immune resistance. In the resistant tumors, TAMs remained inactive and did not exert antigen-presenting activity. Targeted delivery of a long peptide antigen to TAMs by using a nano-sized hydrogel (nanogel) in the presence of a TLR agonist activated TAMs, induced their antigen-presenting activity, and thereby transformed the resistant tumors into tumors sensitive to adaptive immune responses such as adoptive transfer of tumor-specific T cell receptor-engineered T cells. These results indicate that the status and function of TAMs have a significant impact on tumor immune sensitivity and that manipulation of TAM functions would be an effective approach for improving the efficacy of immunotherapies. |
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書誌情報 |
Journal of Clinical Investigation 巻 129, 号 3, p. 1278-1294, 発行日 2019-03-01 |
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出版者 | ||||||
出版者 | American Society for Clinical Investigation | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 00219738 | |||||
EISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 15588238 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | 10.1172/JCI97642 | |||||
権利 | ||||||
権利情報 | c 2019, American Society for Clinical Investigation. | |||||
著者版フラグ | ||||||
出版タイプ | VoR | |||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
引用 | ||||||
内容記述タイプ | Other | |||||
内容記述 | The Journal of clinical investigation, 129(3), pp.1278-1294; 2019 |