| RRC ID |
82153
|
| Author |
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.
|
| Title |
STING activator 2'3'-cGAMP enhanced HSV-1-based oncolytic viral therapy.
|
| Journal |
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.
|
| Volume |
18(5)
|
| Pages |
1259-1277
|
| Published |
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
|
| Resource |
| Human and Animal Cells |
Vero(RCB0001) |
