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Primary Tumor Suppression and Systemic Immune Activation of Macrophages through the Sting Pathway in Metastatic Skin Tumor

Authors
 Chun-Bong Synn  ;  Dong Kwon Kim  ;  Jae Hwan Kim  ;  Youngseon Byeon  ;  Young Seob Kim  ;  Mi Ran Yun  ;  Ji Min Lee  ;  Wongeun Lee  ;  Eun Ji Lee  ;  Seul Lee  ;  You-Won Lee  ;  Doo Jae Lee  ;  Hyun-Woo Kim  ;  Chang Gon Kim  ;  Min Hee Hong  ;  June Dong Park  ;  Sun Min Lim  ;  Kyoung-Ho Pyo 
Citation
 YONSEI MEDICAL JOURNAL, Vol.63(1) : 42-55, 2022-01 
Journal Title
YONSEI MEDICAL JOURNAL
ISSN
 0513-5796 
Issue Date
2022-01
MeSH
Animals ; Immunotherapy ; Macrophages ; Membrane Proteins / genetics ; Memory T Cells* ; Mice ; Skin Neoplasms*
Keywords
STING agonist ; T cell-mediated immune response ; lung cancer ; macrophages ; skin metastasis
Abstract
Purpose: Agonists of the stimulator of interferon genes (STING) play a key role in activating the STING pathway by promoting the production of cytokines. In this study, we investigated the antitumor effects and activation of the systemic immune response of treatment with DMXAA (5,6-dimethylxanthenone-4-acetic acid), a STING agonist, in EML4-ALK lung cancer and CT26 colon cancer.

Materials and methods: The abscopal effects of DMXAA in the treatment of metastatic skin nodules were assessed. EML4-ALK lung cancer and CT26 colon cancer models were used to evaluate these effects after DMXAA treatment. To evaluate the expression of macrophages and T cells, we sacrificed the tumor-bearing mice after DMXAA treatment and obtained the formalin-fixed paraffin-embedded (FFPE) tissue and tumor cells. Immunohistochemistry and flow cytometry were performed to analyze the expression of each FFPE and tumor cell.

Results: We observed that highly infiltrating immune cells downstream of the STING pathway had increased levels of chemokines after DMXAA treatment. In addition, the levels of CD80 and CD86 in antigen-presenting cells were significantly increased after STING activation. Furthermore, innate immune activation altered the systemic T cell-mediated immune responses, induced proliferation of macrophages, inhibited tumor growth, and increased numbers of cytotoxic memory T cells. Tumor-specific lymphocytes also increased in number after treatment with DMXAA.

Conclusion: The abscopal effect of DMXAA treatment on the skin strongly reduced the spread of EML4-ALK lung cancer and CT26 colon cancer through the STING pathway and induced the presentation of antigens.
Files in This Item:
T202300454.pdf Download
DOI
10.3349/ymj.2022.63.1.42
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Young Seob(김영섭)
Kim, Jae Hwan(김재환)
Kim, Chang Gon(김창곤)
Byeon, Yeongseon(변영선)
Lim, Sun Min(임선민)
Pyo, Kyoung Ho(표경호) ORCID logo https://orcid.org/0000-0001-5428-0288
Hong, Min Hee(홍민희) ORCID logo https://orcid.org/0000-0003-3490-2195
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/193003
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