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Dec 17, 2021;23 138-150.

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
Author Information
  1. Seung-Phil Shin: Division of Tumor Immunology, Research Institute & Hospital, National Cancer Center, Goyang, Gyeonggi-do 410-769, Republic of Korea.
  2. A-Ra Goh: Division of Tumor Immunology, Research Institute & Hospital, National Cancer Center, Goyang, Gyeonggi-do 410-769, Republic of Korea.
  3. Ji-Min Ju: Division of Tumor Immunology, Research Institute & Hospital, National Cancer Center, Goyang, Gyeonggi-do 410-769, Republic of Korea.
  4. Hyeon-Gu Kang: Department of Biomedical Science, BK21-Plus Research Team for Bioactive Control Technology, College of Natural Sciences, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 61452, Republic of Korea.
  5. Seok-Jun Kim: Department of Biomedical Science, BK21-Plus Research Team for Bioactive Control Technology, College of Natural Sciences, Chosun University, 309 Pilmun-daero, Dong-gu, Gwangju 61452, Republic of Korea.
  6. Jong-Kwang Kim: Genome Analysis, Team Research Core Center, Research Institute & Hospital, National Cancer Center, Goyang, Republic of Korea.
  7. Eun-Jung Park: Division of Tumor Immunology, Research Institute & Hospital, National Cancer Center, Goyang, Gyeonggi-do 410-769, Republic of Korea.
  8. Yong-Soo Bae: Department of Biological Sciences, SRC Center for Immune Research on Non-lymphoid Organs, Sungkyunkwan University, Jangan-gu, Suwon, Republic of Korea.
  9. Kyungho Choi: Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Republic of Korea.
  10. Yuh-Seog Jung: Division of Tumor Immunology, Research Institute & Hospital, National Cancer Center, Goyang, Gyeonggi-do 410-769, Republic of Korea.
  11. Sang-Jin Lee: Division of Tumor Immunology, Research Institute & Hospital, National Cancer Center, Goyang, Gyeonggi-do 410-769, Republic of Korea.
PMID: 34703882 DOI: 10.1016/j.omto.2021.09.001

Abstract

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 model, C57BL/6 mice were subcutaneously injected with MEER/CD200 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 and . 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.

Keywords

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

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Journal Article

Word Cloud

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