AUTHOR=Bhat Hilal , Zaun Gregor , Hamdan Thamer A. , Lang Judith , Adomati Tom , Schmitz Rosa , Friedrich Sarah-Kim , Bergerhausen Michael , Cham Lamin B. , Li Fanghui , Ali Murtaza , Zhou Fan , Khairnar Vishal , Duhan Vikas , Brandenburg Tim , Machlah Yara Maria , Schiller Maximilian , Berry Arshia , Xu Haifeng , Vollmer Jörg , Häussinger Dieter , Thier Beatrice , Pandyra Aleksandra A. , Schadendorf Dirk , Paschen Annette , Schuler Martin , Lang Philipp A. , Lang Karl S. TITLE=Arenavirus Induced CCL5 Expression Causes NK Cell-Mediated Melanoma Regression JOURNAL=Frontiers in Immunology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.01849 DOI=10.3389/fimmu.2020.01849 ISSN=1664-3224 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.