論文 - 詳細
| RRC ID | 63485 |
|---|---|
| 著者 | Kitahata Y, Kanuma T, Hayashi M, Kobayashi N, Ozasa K, Kusakabe T, Temizoz B, Kuroda E, Yamaue H, Coban C, Yamamoto T, Kobiyama K, Aoshi T, Ishii KJ. |
| タイトル | Circulating nano-particulate TLR9 agonist scouts out tumor microenvironment to release immunogenic dead tumor cells. |
| ジャーナル | Oncotarget |
| Abstract |
Recent evidence suggest that a β-glucan derived from mushroom Schizophyllan(SPG) complexed with a humanized TLR9 agonistic CpG DNA, K3 (K3-SPG) is a promising vaccine adjuvant that induces robust CD8 T cell responses to co-administered antigen. However, it has not been investigated whether K3-SPG alone can act as an anti-cancer immunotherapeutic agent or not. Here, we demonstrate that intravenous injection of K3-SPG, but not CpG alone, is accumulated in the tumor microenvironment and triggered immunogenic cell death (ICD) of tumor cells by local induction of type-I interferon (IFN) as well as IL-12. Resultant innate immune activation as well as subsequent tumor-specific CD8 T cell responses were contributed the tumor growth suppression. This anti-tumor effect of K3-SPG monotherapy was also confirmed by using various tumor models including pancreatic cancer peritoneal dissemination model. Taken together, nano-particulate TLR9 agonist injected intravenously can scout out tumor microenvironment to provoke local innate immune activation and release dead tumor cells into circulation that may induce broader and protective tumor antigen-specific CD8 T cells. |
| 巻・号 | 7(31) |
| ページ | 48860-48869 |
| 公開日 | 2016-8-2 |
| DOI | 10.18632/oncotarget.10379 |
| PII | 10379 |
| PMID | 27384490 |
| PMC | PMC5226476 |
| MeSH | Adjuvants, Immunologic / pharmacology Animals Antibody Formation CD8-Positive T-Lymphocytes / immunology CpG Islands / drug effects Cytokines / pharmacology Humans Immunity, Innate Interferon Type I / pharmacology Interferon-gamma / immunology Interleukin-12 / immunology Leukocyte Common Antigens / metabolism Mice Mice, Inbred C57BL Mice, Transgenic Nanoparticles / chemistry* Neoplasms / blood Neoplasms / immunology* Neoplasms / therapy* Oligodeoxyribonucleotides / administration & dosage Phagocytosis Sizofiran / pharmacology* Toll-Like Receptor 9 / agonists* Tumor Microenvironment / drug effects* |
| IF | 5.168 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | B16F10(RCB2630) |