Oncolytic influenza virus infection restores immunocompetence of lung tumor-associated alveolar macrophages
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 R...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-05-01
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| Series: | OncoImmunology |
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| Online Access: | http://dx.doi.org/10.1080/2162402X.2017.1423171 |
| _version_ | 1811285620260077568 |
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| author | Dörthe Masemann Katharina Köther Meike Kuhlencord Georg Varga Johannes Roth Brian Dennis Lichty Ulf Rüdiger Rapp Viktor Wixler Stephan Ludwig |
| author_facet | Dörthe Masemann Katharina Köther Meike Kuhlencord Georg Varga Johannes Roth Brian Dennis Lichty Ulf Rüdiger Rapp Viktor Wixler Stephan Ludwig |
| author_sort | Dörthe Masemann |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T02:47:44Z |
| format | Article |
| id | doaj.art-7978c9ea44a246c99fae503377d470fc |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-04-13T02:47:44Z |
| publishDate | 2018-05-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-7978c9ea44a246c99fae503377d470fc2022-12-22T03:05:58ZengTaylor & Francis GroupOncoImmunology2162-402X2018-05-017510.1080/2162402X.2017.14231711423171Oncolytic influenza virus infection restores immunocompetence of lung tumor-associated alveolar macrophagesDörthe Masemann0Katharina Köther1Meike Kuhlencord2Georg Varga3Johannes Roth4Brian Dennis Lichty5Ulf Rüdiger Rapp6Viktor Wixler7Stephan Ludwig8Institute of Virology (IMV), Westfaelische-Wilhelms UniversityInstitute of Virology (IMV), Westfaelische-Wilhelms UniversityInstitute of Immunology, Westfaelische-Wilhelms UniversityRheumatology and Immunology, University Children´s Hospital MuensterInstitute of Immunology, Westfaelische-Wilhelms UniversityMcMaster Immunology Research Centre, McMaster UniversityMax Planck Institute for Heart and Lung ResearchInstitute of Virology (IMV), Westfaelische-Wilhelms UniversityInstitute of Virology (IMV), Westfaelische-Wilhelms UniversityNon-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.http://dx.doi.org/10.1080/2162402X.2017.1423171influenza a viruseslung canceroncolytic virusesimmunotherapyvirotherapyimmune cell polarizationtumor-associated macrophages |
| spellingShingle | Dörthe Masemann Katharina Köther Meike Kuhlencord Georg Varga Johannes Roth Brian Dennis Lichty Ulf Rüdiger Rapp Viktor Wixler Stephan Ludwig Oncolytic influenza virus infection restores immunocompetence of lung tumor-associated alveolar macrophages OncoImmunology influenza a viruses lung cancer oncolytic viruses immunotherapy virotherapy immune cell polarization tumor-associated macrophages |
| title | Oncolytic influenza virus infection restores immunocompetence of lung tumor-associated alveolar macrophages |
| title_full | Oncolytic influenza virus infection restores immunocompetence of lung tumor-associated alveolar macrophages |
| title_fullStr | Oncolytic influenza virus infection restores immunocompetence of lung tumor-associated alveolar macrophages |
| title_full_unstemmed | Oncolytic influenza virus infection restores immunocompetence of lung tumor-associated alveolar macrophages |
| title_short | Oncolytic influenza virus infection restores immunocompetence of lung tumor-associated alveolar macrophages |
| title_sort | oncolytic influenza virus infection restores immunocompetence of lung tumor associated alveolar macrophages |
| topic | influenza a viruses lung cancer oncolytic viruses immunotherapy virotherapy immune cell polarization tumor-associated macrophages |
| url | http://dx.doi.org/10.1080/2162402X.2017.1423171 |
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