FcγRI expression on macrophages is required for antibodymediated tumor protection by cytomegalovirus-based vaccines

Hreinn Benonisson, Heng Sheng Sow, Cor Breukel, Jill W. C. Claassens, Conny Brouwers, Margot M. Linssen, Anke Redeker, Marieke F. Fransen, Thorbald van Hall, Ferry Ossendorp, Ramon Arens, Sjef Verbeek

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Cytomegalovirus (CMV)-based vaccine vectors are promising vaccine platforms because they induce strong and long-lasting immune responses. Recently it has been shown that vaccination with a mouse CMV (MCMV) vector expressing the melanomaspecific antigen TRP2 (MCMV-TRP2) protects mice against outgrowth of TRP2-positive B16 melanoma tumors, and this protection was dependent on the induction of IgG antibodies. Here we demonstrate that, although mice lacking all receptors for the Fc part of IgG (FcγRs) develop normal IgG responses after MCMV-TRP2 vaccination, the protection against B16 melanoma was completely abrogated, indicating that FcγRs are indispensable in the downstream effector pathway of the polyclonal anti-TRP2 antibody response. By investigating compound FcγR-deficient mouse strains and by using immune cell type-specific cell ablation we show that the IgG antibody-mediated tumor protection elicited by MCMV-TRP2 mainly depends on FcγRI expression on macrophages, whereas FcγRIV plays only a modest role. Thus, tumor-specific antibody therapy might benefit from combination therapy that recruits FcγRI-expressing proinflammatory macrophages to the tumor micro-environment.
Original languageEnglish
Pages (from-to)29392-29402
JournalOncotarget
Volume9
Issue number50
DOIs
Publication statusPublished - 2018
Externally publishedYes

Cite this

Benonisson, H., Sow, H. S., Breukel, C., Claassens, J. W. C., Brouwers, C., Linssen, M. M., ... Verbeek, S. (2018). FcγRI expression on macrophages is required for antibodymediated tumor protection by cytomegalovirus-based vaccines. Oncotarget, 9(50), 29392-29402. https://doi.org/10.18632/oncotarget.25630