title: Cell surface receptor FPR2 promotes antitumor host defense by limiting M2 polarization of macrophages.
abstract: FPR2 (Fpr2 in mouse) is a G-protein-coupled receptor interacting with bacterial and host-derived chemotactic agonists. Fpr2 supports innate and adaptive immune responses as illustrated by the reduction in severity of allergic airway inflammation in Fpr2-KO mice, due to impaired trafficking of antigen-presenting dendritic cells (DC). The aim of this study is to examine the role of Fpr2 in host antitumor responses. We found that Fpr2-KO mice bearing subcutaneously implanted Lewis lung carcinoma (LLC) cells exhibited significantly shortened survival than normal mice due to more rapidly growing tumors. In contrast, in Fpr2-transgenic mice overexpressing Fpr2, subcutaneously implanted LLC tumors grew more slowly than those in wild-type (WT) littermates. Investigation of tumor tissues revealed an increased number of macrophages associated with tumors grown in Fpr2-KO mice. Macrophages derived from Fpr2-KO mice showed a more potent chemotactic response to LLC-derived supernatant (LLC Sup), which could be neutralized by an anti-CCL2 antibody. The increased chemotaxis of Fpr2-KO mouse macrophages in response to LLC Sup was due to their higher level expression of CCR4, a chemokine receptor that also recognizes the ligand CCL2. Furthermore, macrophages from Fpr2-KO mice acquired an M2 phenotype after stimulation with LLC Sup. These results suggest that Fpr2 plays an important role in host defense against implanted LLC by sustaining macrophages in an M1 phenotype with more potent antitumor activities.
authors.affiliation: Laboratory of Molecular Immunoregulation, Cancer Inflammation Program, Center of Cancer Research, National Cancer Institute-Frederick, NIH, Frederick, Maryland 21702, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Keqiang
authors.initials: K
authors.lastname: Chen
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wang
authors.forename: Wanghua
authors.initials: W
authors.lastname: Gong
authors.forename: Teizo
authors.initials: T
authors.lastname: Yoshimura
authors.forename: Mingyong
authors.initials: M
authors.lastname: Liu
authors.forename: Ji Ming
authors.initials: JM
authors.lastname: Wang
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000276:immunology* / Q000401:mortality; D002633:Chemotaxis; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D010641:Phenotype; D044042:Receptors, Formyl Peptide / Q000235:genetics / Q000502:physiology*
chemical_list: D044042:Receptors, Formyl Peptide; C481578:formyl peptide receptor 2, mouse