Frontiers in Immunology (Aug 2020)
Arenavirus Induced CCL5 Expression Causes NK Cell-Mediated Melanoma Regression
- Hilal Bhat,
- Gregor Zaun,
- Thamer A. Hamdan,
- Judith Lang,
- Tom Adomati,
- Rosa Schmitz,
- Sarah-Kim Friedrich,
- Michael Bergerhausen,
- Lamin B. Cham,
- Fanghui Li,
- Murtaza Ali,
- Fan Zhou,
- Vishal Khairnar,
- Vishal Khairnar,
- Vikas Duhan,
- Tim Brandenburg,
- Yara Maria Machlah,
- Maximilian Schiller,
- Arshia Berry,
- Haifeng Xu,
- Jörg Vollmer,
- Dieter Häussinger,
- Beatrice Thier,
- Aleksandra A. Pandyra,
- Aleksandra A. Pandyra,
- Dirk Schadendorf,
- Dirk Schadendorf,
- Annette Paschen,
- Annette Paschen,
- Martin Schuler,
- Martin Schuler,
- Philipp A. Lang,
- Karl S. Lang
Affiliations
- Hilal Bhat
- Medical Faculty, Institute of Immunology, University Duisburg-Essen, Essen, Germany
- Gregor Zaun
- Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Thamer A. Hamdan
- Medical Faculty, Institute of Immunology, University Duisburg-Essen, Essen, Germany
- Judith Lang
- Medical Faculty, Institute of Immunology, University Duisburg-Essen, Essen, Germany
- Tom Adomati
- Medical Faculty, Institute of Immunology, University Duisburg-Essen, Essen, Germany
- Rosa Schmitz
- Medical Faculty, Institute of Immunology, University Duisburg-Essen, Essen, Germany
- Sarah-Kim Friedrich
- Medical Faculty, Institute of Immunology, University Duisburg-Essen, Essen, Germany
- Michael Bergerhausen
- Medical Faculty, Institute of Immunology, University Duisburg-Essen, Essen, Germany
- Lamin B. Cham
- Medical Faculty, Institute of Immunology, University Duisburg-Essen, Essen, Germany
- Fanghui Li
- Medical Faculty, Institute of Immunology, University Duisburg-Essen, Essen, Germany
- Murtaza Ali
- Medical Faculty, Institute of Immunology, University Duisburg-Essen, Essen, Germany
- Fan Zhou
- Medical Faculty, Institute of Immunology, University Duisburg-Essen, Essen, Germany
- Vishal Khairnar
- Medical Faculty, Institute of Immunology, University Duisburg-Essen, Essen, Germany
- Vishal Khairnar
- Department of Systems Biology, Beckman Research Institute, City of Hope, Monrovia, CA, United States
- Vikas Duhan
- Medical Faculty, Institute of Immunology, University Duisburg-Essen, Essen, Germany
- Tim Brandenburg
- Medical Faculty, Institute of Immunology, University Duisburg-Essen, Essen, Germany
- Yara Maria Machlah
- Medical Faculty, Institute of Immunology, University Duisburg-Essen, Essen, Germany
- Maximilian Schiller
- Medical Faculty, Institute of Immunology, University Duisburg-Essen, Essen, Germany
- Arshia Berry
- Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
- Haifeng Xu
- Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
- Jörg Vollmer
- Abalos Therapeutics GmbH, Essen, Germany
- Dieter Häussinger
- Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Düsseldorf, Germany
- Beatrice Thier
- Department of Dermatology, University Hospital Essen, Essen, Germany
- Aleksandra A. Pandyra
- Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
- Aleksandra A. Pandyra
- Department of Gastroenterology, Hepatology and Infectious Diseases, University of Düsseldorf, Düsseldorf, Germany
- Dirk Schadendorf
- Department of Dermatology, University Hospital Essen, Essen, Germany
- Dirk Schadendorf
- German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany
- Annette Paschen
- Department of Dermatology, University Hospital Essen, Essen, Germany
- Annette Paschen
- German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany
- Martin Schuler
- Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Essen, Germany
- Martin Schuler
- German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany
- Philipp A. Lang
- Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
- Karl S. Lang
- Medical Faculty, Institute of Immunology, University Duisburg-Essen, Essen, Germany
- DOI
- https://doi.org/10.3389/fimmu.2020.01849
- Journal volume & issue
-
Vol. 11
Abstract
Immune activation within the tumor microenvironment is one promising approach to induce tumor regression. Certain viruses including oncolytic viruses such as the herpes simplex virus (HSV) and non-oncolytic viruses such as the lymphocytic choriomeningitis virus (LCMV) are potent tools to induce tumor-specific immune activation. However, not all tumor types respond to viro- and/or immunotherapy and mechanisms accounting for such differences remain to be defined. In our current investigation, we used the non-cytopathic LCMV in different human melanoma models and found that melanoma cell lines produced high levels of CCL5 in response to immunotherapy. In vivo, robust CCL5 production in LCMV infected Ma-Mel-86a tumor bearing mice led to recruitment of NK cells and fast tumor regression. Lack of NK cells or CCL5 abolished the anti-tumoral effects of immunotherapy. In conclusion, we identified CCL5 and NK cell-mediated cytotoxicity as new factors influencing melanoma regression during virotherapy.
Keywords
