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=Volume 11 - 2020

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 is one promising approach to induce immune-mediated tumor regression. Certain viruses including oncolytic viruses like herpes simplex virus (HSV) and non-oncolytic viruses such as 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 explaining such differences remain to be defined. We used the non-cytopathic LCMV in different human melanoma tumor 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 as induced by the inhibitor Maraviroc abolished anti-tumoral effects of immunotherapy. In conclusion, we identified CCL5 and NK cell-mediated cytotoxicity as new factors influencing melanoma regression during virotherapy.