Oncolytic influenza virus infection restores immunocompetence of lung tumor-associated alveolar macrophages
| Autor: | Stephan Ludwig, Katharina Köther, Dörthe Masemann, Viktor Wixler, Georg Varga, Brian D. Lichty, Meike Kuhlencord, Ulf R. Rapp, Johannes Roth |
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| Rok vydání: | 2018 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
0301 basic medicine influenza a viruses medicine.medical_treatment Immunology immune cell polarization medicine.disease_cause lcsh:RC254-282 03 medical and health sciences 0302 clinical medicine Immune system Influenza A virus Immunology and Allergy Medicine Virotherapy Lung cancer Original Research Tumor microenvironment tumor-associated macrophages business.industry Immunotherapy lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease respiratory tract diseases Oncolytic virus lung cancer 030104 developmental biology Oncology oncolytic viruses 030220 oncology & carcinogenesis Cancer research immunotherapy virotherapy Immunocompetence lcsh:RC581-607 business |
| Zdroj: | OncoImmunology, Vol 7, Iss 5 (2018) Oncoimmunology |
| ISSN: | 2162-402X |
| Popis: | Non-small-cell lung cancer (NSCLC) is the most frequent type of lung cancer and demonstrates high resistance to radiation and chemotherapy. These tumors evade immune system detection by promoting an immunosuppressive tumor microenvironment. Genetic analysis has revealed oncogenic activation of the Ras/Raf/MEK/ERK signaling pathway to be a hallmark of NSCLCs, which promotes influenza A virus (IAV) infection and replication in these cells. Thus, we aimed to unravel the oncolytic properties of IAV infection against NSCLCs in an immunocompetent model in vivo. Using Raf-BxB transgenic mice that spontaneously develop NSCLCs, we demonstrated that infection with low-pathogenic IAV leads to rapid and efficient oncolysis, eliminating 70% of the initial tumor mass. Interestingly, IAV infection of Raf-BxB mice caused a functional reversion of immunosuppressed tumor-associated lung macrophages into a M1-like pro-inflammatory active phenotype that additionally supported virus-induced oncolysis of cancer cells. Altogether, our data demonstrate for the first time in an immunocompetent in vivo model that oncolytic IAV infection is capable of restoring and redirecting immune cell functions within the tumor microenvironment of NSCLCs. |
| Databáze: | OpenAIRE |
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