Fc?RI expression on macrophages is required for antibody-mediated tumor protection by cytomegalovirus-based vaccines.

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 (Fc?Rs) develop normal IgG responses after MCMV-TRP2 vaccination, the protection against B16 melanoma was completely abrogated, indicating that Fc?Rs are indispensable in the downstream effector pathway of the polyclonal anti-TRP2 antibody response. By investigating compound Fc?R-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 Fc?RI expression on macrophages, whereas Fc?RIV plays only a modest role. Thus, tumor-specific antibody therapy might benefit from combination therapy that recruits Fc?RI-expressing pro-inflammatory macrophages to the tumor micro-environment.

SUBMITTER: Benonisson H 

PROVIDER: S-EPMC6047664 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature