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Local, multimodal intralesional therapy renders distant brain metastases susceptible to PD-L1 blockade in a preclinical model of triple-negative breast cancer.
http://hdl.handle.net/10422/00013127
http://hdl.handle.net/10422/00013127ae308230-c7ea-4987-ae4a-abc2ea5635fc
名前 / ファイル | ライセンス | アクション |
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s41598-021-01455-4 (4.5 MB)
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This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2021-11-17 | |||||
タイトル | ||||||
タイトル | Local, multimodal intralesional therapy renders distant brain metastases susceptible to PD-L1 blockade in a preclinical model of triple-negative breast cancer. | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Immunotherapy | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Tumour immunology | |||||
キーワード | ||||||
言語 | en | |||||
主題Scheme | Other | |||||
主題 | Vaccines | |||||
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 |
YOKOI, Toshihiro
× YOKOI, Toshihiro× OBA, Takaaki× KAJIHARA, Ryutaro× ABRAMS, Scott I.× ITO, Fumito |
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著者別名 |
横井, 俊浩
× 横井, 俊浩 |
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抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Despite recent progress in therapeutic strategies, prognosis of metastatic triple-negative breast cancer (TNBC) remains dismal. Evidence suggests that the induction and activation of tumor-residing conventional type-1 dendritic cells (cDC1s) is critical for the generation of CD8+ T cells that mediate the regression of mammary tumors and potentiate anti-PD-1/PD-L1 therapeutic efficacy. However, it remains unknown whether this strategy is effective against metastatic TNBC, which is poorly responsive to immunotherapy. Here, using a mouse model of TNBC, we established orthotopic mammary tumors and brain metastases, and treated mammary tumors with in situ immunomodulation (ISIM) consisting of intratumoral injections of Flt3L to mobilize cDC1s, local irradiation to induce immunogenic tumor cell death, and TLR3/CD40 stimulation to activate cDC1s. ISIM treatment of the mammary tumor increased circulating T cells with effector phenotypes, and infiltration of CD8+ T cells into the metastatic brain lesions, resulting in delayed progression of brain metastases and improved survival. Furthermore, although anti-PD-L1 therapy alone was ineffective against brain metastases, ISIM overcame resistance to anti-PD-L1 therapy, which rendered these tumor-bearing mice responsive to anti-PD-L1 therapy and further improved survival. Collectively, these results illustrate the therapeutic potential of multimodal intralesional therapy for patients with unresectable and metastatic TNBC. | |||||
書誌情報 |
en : Scientific Reports 巻 11, 号 1, 発行日 2021-11-09 |
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出版者 | ||||||
出版者 | Springer Nature | |||||
ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 2045-2322 | |||||
PMID | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | PMID | |||||
関連識別子 | 34754037 | |||||
PMCID | ||||||
識別子タイプ | URI | |||||
関連識別子 | http://www.ncbi.nlm.nih.gov/pmc/articles/pmc8578367/ | |||||
関連名称 | PMC8578367 | |||||
DOI | ||||||
関連タイプ | isIdenticalTo | |||||
識別子タイプ | DOI | |||||
関連識別子 | https://doi.org/10.1038/s41598-021-01455-4 | |||||
関連名称 | 10.1038/s41598-021-01455-4 | |||||
権利 | ||||||
権利情報 | © The Author(s) 2021 | |||||
フォーマット | ||||||
内容記述タイプ | Other | |||||
内容記述 | ||||||
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 | |||||
資源タイプ | ||||||
内容記述タイプ | Other | |||||
内容記述 | Journal Article |