論文 - 詳細
| RRC ID | 82153 |
|---|---|
| 著者 | Sibal PA, Matsumura S, Ichinose T, Bustos-Villalobos I, Morimoto D, Eissa IR, Abdelmoneim M, Aboalela MAM, Mukoyama N, Tanaka M, Naoe Y, Kasuya H. |
| タイトル | STING activator 2'3'-cGAMP enhanced HSV-1-based oncolytic viral therapy. |
| ジャーナル | Mol Oncol |
| Abstract |
Oncolytic viruses (OVs) can selectively replicate in tumor cells and remodel the microenvironment of immunologically cold tumors, making them a promising strategy to evoke antitumor immunity. Similarly, agonists of the stimulator of interferon genes (STING)-interferon (IFN) pathway, the main cellular antiviral system, provide antitumor benefits by inducing the activation of dendritic cells (DC). Considering how the activation of the STING-IFN pathway could potentially inhibit OV replication, the use of STING agonists alongside OV therapy remains largely unexplored. Here, we explored the antitumor efficacy of combining an HSV-1-based OV, C-REV, with a membrane-impermeable STING agonist, 2'3'-GAMP. Our results demonstrated that tumor cells harbor a largely defective STING-IFN pathway, thereby preventing significant antiviral IFN induction regardless of the permeability of the STING agonist. In vivo, the combination therapy induced more proliferative KLRG1-high PD1-low CD8+ T-cells and activated CD103+ DC in the tumor site and increased tumor-specific CD44+ CD8+ T-cells in the lymph node. Overall, the combination therapy of C-REV with 2'3'-cGAMP elicited antitumor immune memory responses and significantly enhanced systemic antitumor immunity in both treated and non-treated distal tumors. |
| 巻・号 | 18(5) |
| ページ | 1259-1277 |
| 公開日 | 2024-5-1 |
| DOI | 10.1002/1878-0261.13603 |
| PMID | 38400597 |
| PMC | PMC11076993 |
| MeSH | Animals CD8-Positive T-Lymphocytes / immunology Cell Line, Tumor Combined Modality Therapy / methods Dendritic Cells / immunology Female Herpesvirus 1, Human* Humans Membrane Proteins* / metabolism Mice Mice, Inbred C3H Mice, Inbred C57BL Nucleotides, Cyclic* Oncolytic Virotherapy* / methods Oncolytic Viruses / genetics |
| IF | 6.574 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 3 |
| 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 | Vero(RCB0001) |