Oncotarget

Research Papers:

FcγRI expression on macrophages is required for antibody-mediated 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 and Sjef Verbeek _

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Oncotarget. 2018; 9:29392-29402. https://doi.org/10.18632/oncotarget.25630

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Abstract

Hreinn Benonisson1, Heng Sheng Sow1, Cor Breukel1, Jill W.C. Claassens1, Conny Brouwers1, Margot M. Linssen1, Anke Redeker2, Marieke F. Fransen2, Thorbald van Hall3, Ferry Ossendorp2, Ramon Arens2,* and Sjef Verbeek1,*

1Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

2Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands

3Department of Medical Oncology, Leiden University Medical Center, Leiden, The Netherlands

*These authors contributed equally to this work

Correspondence to:

Sjef Verbeek, email: [email protected]

Ramon Arens, email: [email protected]

Keywords: melanoma; Fc receptors; antibody; cytomegalovirus; vaccines

Received: February 16, 2018     Accepted: June 03, 2018     Published: June 29, 2018

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 melanoma-specific 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 pro-inflammatory macrophages to the tumor micro-environment.


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