Activity-regulated cytoskeleton-associated protein/activity-regulated gene 3.1 (Arc/Arg3.1) enhances dendritic cell vaccination in experimental melanoma

Xin-Wen Zhang; Katrin Huck; Kristine Jähne; Frederik Cichon; Jana K Sonner; Friederike Ufer; Simone Bauer; Marcel Seungsu Woo; Ed Green; Kevin Lu; Michael Kilian; Manuel A Friese; Michael Platten; Katharina Sahm

doi:10.1080/2162402X.2021.1920739

Activity-regulated cytoskeleton-associated protein/activity-regulated gene 3.1 (Arc/Arg3.1) enhances dendritic cell vaccination in experimental melanoma

Oncoimmunology. 2021 May 14;10(1):1920739. doi: 10.1080/2162402X.2021.1920739.

Authors

Xin-Wen Zhang^{1

2}, Katrin Huck^{1

2}, Kristine Jähne^{1

2}, Frederik Cichon^{1

2}, Jana K Sonner^{1

2}, Friederike Ufer³, Simone Bauer³, Marcel Seungsu Woo³, Ed Green^{1

2}, Kevin Lu^{1

2}, Michael Kilian^{1

2}, Manuel A Friese³, Michael Platten^{1

2}, Katharina Sahm^{1

2}

Affiliations

¹ Department of Neurology, Mannheim Medical Center, University of Heidelberg, Mannheim, Germany.
² DKTK Clinical Cooperation Unit Neuroimmunology and Brain Tumor Immunology, German Cancer Research Center, Heidelberg, Germany.
³ Institute of Neuroimmunology Und Multiple Sclerosis, Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Abstract

Dendritic cell (DC) vaccination has proven to be an effective and safe adjuvant for cancer immunotherapies. As the presence of DCs within the tumor microenvironment promotes adaptive antitumor immunity, enhancement of DC migration toward the tumor microenvironment following DC vaccination might represent one possible approach to increase its therapeutic efficacy. While recent findings suggest the activity-regulated cytoskeleton-associated protein/activity-regulated gene 3.1 (Arc/Arg3.1) as critical regulator of DC migration in the context of autoimmune diseases, we aimed to investigate the impact of Arc/Arg3.1 expression for DC-based cancer vaccines. To this end, DC migration capacity as well as the induction of T cell-mediated antitumor immunity was assessed in an experimental B16 melanoma model with Arc/Arg3.1^-/- and Arc/Arg3.1-expressing BMDCs applied as a subcutaneous vaccine. While antigen presentation on DCs was critical for unleashing effective T cell mediated antitumor immune responses, Arc/Arg3.1 expression enhanced DC migration toward the tumor and secondary lymphoid organs. Moreover, Arc/Arg3.1-expressing BMDCs shape the tumor immune microenvironment by facilitating tumor recruitment of antigen-specific effector T cells. Thus, Arc/Arg3.1 may represent a novel therapeutic target in DCs in order to increase the therapeutic efficacy of DC vaccination.

Keywords: Adoptive immunotherapy; CD8-positive T-lymphocytes; dendritic cells; melanoma; tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cancer Vaccines*
Cytoskeleton
Dendritic Cells
Melanoma, Experimental* / genetics
Mice
Mice, Inbred C57BL
Tumor Microenvironment
Vaccination

Substances

Cancer Vaccines

Grants and funding

This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB1366-TPC01, Project number: 394046768, to K.S. and M.P, PL-315/8-1 to M.P.), the Helmholtz Association (ZT00-27 to M.P.), the DKFZ-MOST Program (Ca-188 to M.P.), the German Cancer Aid (70113515 to M.P., 70113115 to X.W.Z.), the Hertie Foundation (P1200013 to K.S.), the Helmholtz International Graduate School for Cancer Research and the Graduate Academy Baden-Wurttemberg to M.K. and F.C.