Studying infection with oncolytic influenza A virus (IAV) in an immunocompetent Raf-BxB spontaneous NSCLC murine model, Masemann et al. observed that infection with IAV not only directly decreased the number and size of lung tumors via viral lytic growth, but also restored the pro-inflammatory and anti-tumoral effects of previously tumor-suppressed alveolar macrophages in the lungs in vivo. Infection caused a shift in the tissue resident M2-like macrophage to an iNOS+, MHCII+ anti-tumor phenotype.
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.
Author Info: (1) Institute of Virology (IMV), Westfaelische-Wilhelms University, Muenster, Germany. Cluster of Excellence "Cells in Motion", University of Muenster, Muenster, Germany. (2) Insti
Author Info: (1) Institute of Virology (IMV), Westfaelische-Wilhelms University, Muenster, Germany. Cluster of Excellence "Cells in Motion", University of Muenster, Muenster, Germany. (2) Institute of Virology (IMV), Westfaelische-Wilhelms University, Muenster, Germany. Rentschler Biotechnologie GmbH, Laupheim, Germany. (3) Institute of Immunology, Westfaelische-Wilhelms University, Muenster, Germany. (4) Department of Pediatric, Rheumatology and Immunology, University Children s Hospital Muenster, Muenster, Germany. (5) Institute of Immunology, Westfaelische-Wilhelms University, Muenster, Germany. Cluster of Excellence "Cells in Motion", University of Muenster, Muenster, Germany. (6) Department of Pathology and Molecular Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, Ontario, Canada. (7) Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany. (8) Institute of Virology (IMV), Westfaelische-Wilhelms University, Muenster, Germany. Cluster of Excellence "Cells in Motion", University of Muenster, Muenster, Germany. (9) Institute of Virology (IMV), Westfaelische-Wilhelms University, Muenster, Germany. Cluster of Excellence "Cells in Motion", University of Muenster, Muenster, Germany.
