Local adenoviral delivery of soluble CD200R-Ig enhances antitumor immunity by inhibiting CD200-β-catenin-driven M2 macrophage

Seung Phil Shin, A. Ra Goh, Ji Min Ju, Hyeon Gu Kang, Seok Jun Kim, Jong Kwang Kim, Eun Jung Park, Yong Soo Bae, Kyungho Choi, Yuh Seog Jung, Sang Jin Lee

Research output: Contribution to journalArticlepeer-review

1 Scopus citations


CD200 is known as an immune checkpoint molecule that inhibits innate immune cell activation. Using a head and neck squamous cell carcinoma (HNSCC) model, we sought to determine whether localized delivery of adenovirus-expressing sCD200R1-Ig, the soluble extracellular domain of CD200R1, enhances antitumor immunity. Mouse-derived bone marrow cells and M1/M2-like macrophages were cocultured with tumor cells and analyzed for macrophage polarization. As an in vivo model, C57BL/6 mice were subcutaneously injected with MEER/CD200High cells, CD200-overexpressing mouse HNSCC cells. Adenovirus-expressing sCD200R1-Ig (Ad5sCD200R1) was designed, and its effect was tested. Components in the tumor-immune microenvironment (TIME) were quantified using flow cytometry. CD200 promoted tumor growth and induced the expression of immune-related genes, especially macrophage colony-stimulating factor (M-CSF). Interestingly, CD200 induced M2-like polarization both in vitro and in vivo. Consequently, CD200 recruited more regulatory T (Treg) cells and fewer CD8+ effector T cells. These effects were effectively abolished by local injection of Ad5sCD200R1. These protumor effects of CD200 were driven through the β-catenin/NF-κB/M-CSF axis. CD200 upregulated PD-L1, and the combined targeting of CD200 and PD-1 thus showed synergy. The immune checkpoint CD200 upregulated immune-related genes through β-catenin signaling, reprogrammed the TIME, and exerted protumor effects. Ad5sCD200R1 injection could be an effective targeted strategy to enhance antitumor immunoediting.

Original languageEnglish
Pages (from-to)138-150
Number of pages13
JournalMolecular Therapy - Oncolytics
StatePublished - 17 Dec 2021


  • CD200
  • M-CSF
  • M2-like macrophage
  • NF-κB
  • PD-L1
  • β-catenin


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