Recruitment of Intratumoral CD103+ Dendritic Cells by a CXCR4 Antagonist-Armed Virotherapy Enhances Antitumor Immunity
| Autor: | Mateusz Opyrchal, Kunle Odunsi, Aimin Jiang, Hanna Rokita, Danuta Kozbor, Matthew A. Graczyk, Margaret Gil, Marcin P. Komorowski, Anna Mistarz |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Cancer Research CXCR4 antagonist T cells chemical and pharmacologic phenomena lcsh:RC254-282 Article 03 medical and health sciences 0302 clinical medicine Medicine Cytotoxic T cell Pharmacology (medical) dendritic cells Virotherapy Tumor microenvironment business.industry hemic and immune systems Dendritic cell lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Acquired immune system Tumor antigen 3. Good health Oncolytic virus 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer research Molecular Medicine Cancer vaccine virotherapy cancer vaccine business |
| Zdroj: | Molecular Therapy Oncolytics Molecular Therapy: Oncolytics, Vol 14, Iss, Pp 233-245 (2019) |
| ISSN: | 2372-7705 |
| DOI: | 10.1016/j.omto.2019.06.003 |
| Popis: | Intratumoral dendritic cells play an important role in stimulating cytotoxic T cells and driving antitumor immunity. Using a metastatic ovarian tumor model in syngeneic mice, we explored whether therapy with a CXCR4 antagonist-armed oncolytic vaccinia virus activates endogenous CD103+ dendritic cell responses associated with the induction of adaptive immunity against viral and tumor antigens. The overall goal of this study was to determine whether expansion of CD103+ dendritic cells by the virally delivered CXCR4 antagonist augments overall survival and in situ boosting with a tumor antigen peptide-based vaccine. We found that locoregional delivery of the CXCR4-A-armed virus reduced the tumor load and the immunosuppressive network in the tumor microenvironment, leading to infiltration of CD103+ dendritic cells that were capable of phagocytic clearance of cellular material from virally infected cancer cells. Further expansion of tumor-resident CD103+ DCs by injecting the FMS-related tyrosine kinase 3 ligand, the formative cytokine for CD103+ DCs, provided a platform for a booster immunization with the Wilms tumor antigen 1 peptide-based vaccine delivered intraperitoneally with polyriboinosinic:polyribocytidylic acid as an adjuvant. The vaccine-induced antitumor responses inhibited tumor growth and increased overall survival, indicating that expansion of intratumoral CD103+ dendritic cells by CXCR4-A-armed oncovirotherapy treatment can potentiate in situ cancer vaccine boosting. Keywords: virotherapy, CXCR4 antagonist, cancer vaccine, dendritic cells, T cells |
| Databáze: | OpenAIRE |
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