The G protein-coupled receptor mFPR2 promotes anti-tumor host defense (161.7)

Abstract

Abstract Abstract mFPR2 is a G protein-coupled receptor interacting with bacterial and host-derived chemotactic agonists. In vivo, mFPR2 plays a major role in innate and adaptive immune responses as shown by reduced severity of allergic airway inflammation in mFPR2-KO mice due to impaired trafficking of antigen presenting dendritic cells (DCs). The aim of this study is to examine the role of mFPR2 in anti-tumor host responses. We found that mFPR2-KO mice bearing subcutaneously implanted Lewis lung cancer (LLC) cells exhibited significantly shortened survival due to more rapidly growing tumors. In contrast, in mFPR2-transgenic (Tg) mice, subcutaneously implanted LLC tumors grew more slowly than those in wild type (WT) littermates. Mechanistic studies revealed an increased number of macrophages associated with tumors grown in mFPR2 KO mice and macrophages derived from mFPR2 KO mice showed a more potent chemotactic response to LLC-derived supernatant (LLC Sup), which could be neutralized by an anti-CCL2 antibody. In addition, macrophages from mFPR2 KO mice were more prone to assume an M2 phenotype after incubation with LLC Sup. These results suggest that mFPR2 plays an important role in host defense against tumor by sustaining macrophages in an M1 phenotype.