HSV oncolytic therapy upregulates interferon-inducible chemokines and recruits immune effector cells in ovarian cancer
| Autor: | Maria C. Courreges, Richard G. Carroll, Ronald J. Buckanovich, Nigel W. Fraser, Fabian Benencia, Alisha Mohamed-Hadley, Jose R. Conejo-Garcia, George Coukos, Lin Zhang |
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| Rok vydání: | 2005 |
| Předmět: |
Chemokine
CD8-Positive T-Lymphocytes Biology Lymphocyte Activation CXCR3 Mice 03 medical and health sciences 0302 clinical medicine Immune system Interferon Drug Discovery Genetics medicine Animals Humans Simplexvirus IL-2 receptor Molecular Biology 030304 developmental biology Ovarian Neoplasms Pharmacology Mice Inbred BALB C 0303 health sciences Genetic Therapy Up-Regulation 3. Good health Oncolytic virus Chemotaxis Leukocyte 030220 oncology & carcinogenesis Immunology biology.protein Molecular Medicine Female Receptors Chemokine Interferons Chemokines Antibody CD8 medicine.drug |
| Zdroj: | Molecular Therapy. 12:789-802 |
| ISSN: | 1525-0016 |
| DOI: | 10.1016/j.ymthe.2005.03.026 |
| Popis: | Cooperation between oncolytic herpes simplex virus (HSV) and host effector immune mechanisms has been previously described. In the present study, we investigated the mechanism underlying such cooperation in a murine syngeneic model of ovarian carcinoma. Therapeutic administration of HSV-1716, a replication-restricted mutant, resulted in significant reduction of tumor growth and a significant survival advantage. Intratumoral injection of HSV-1716 induced expression of IFN-gamma, MIG, and IP-10 in the tumor. This was accompanied by a significant increase in the number of tumor-associated NK and CD8+ T cells expressing CXCR3 and CD25. Ascites from HSV-1716-treated animals efficiently induced in vitro migration of NK and CD8+ T cells, which was dependent on the presence of MIG and IP-10. Murine monocytes and dendritic cells (DCs) were responsible for the production of MIG and IP-10 upon HSV-1716 infection. In monocytes, this was partially abrogated by neutralizing antibodies against IFN-alpha and -beta, thus indicating a role for type-1 IFNs in the reported effect. Human ovarian carcinomas showed high numbers of monocytes and DCs. Upon HSV-1716 infection, human monocyte-derived DCs produced large amounts of IFN-gamma and upregulated MIG and IP-10 expression. These results indicate that HSV-1716 induces an inflammatory response that may facilitate antitumor immune response upon oncolytic therapy. |
| Databáze: | OpenAIRE |
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