Accelerating and protective effects toward cancer growth in cGAS and FcgRIIb deficient mice, respectively, an impact of macrophage polarization
2
Issued Date
2025-12-01
Resource Type
ISSN
10233830
eISSN
1420908X
Scopus ID
2-s2.0-105003473099
Journal Title
Inflammation Research
Volume
74
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Inflammation Research Vol.74 No.1 (2025)
Suggested Citation
Thim-uam A., Chantawichitwong P., Phuengmaung P., Kaewduangduen W., Saisorn W., Kumpunya S., Pisitkun T., Pisitkun P., Leelahavanichkul A. Accelerating and protective effects toward cancer growth in cGAS and FcgRIIb deficient mice, respectively, an impact of macrophage polarization. Inflammation Research Vol.74 No.1 (2025). doi:10.1007/s00011-025-02036-1 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/109920
Title
Accelerating and protective effects toward cancer growth in cGAS and FcgRIIb deficient mice, respectively, an impact of macrophage polarization
Corresponding Author(s)
Other Contributor(s)
Abstract
Background: Due to the possible influence of inflammation and gut microbiota in cancers. Methods: Fc gamma receptor IIb deficient (FcGRIIb−/−) and cyclic GMP-AMP synthase deficient (cGAS−/−) mice, the model with hyperinflammation and hypo-inflammation, respectively, were subcutaneously injected with MC38 cells (a murine colon cancer cell line). Results: As such, the tumor burdens were most prominent in cGAS−/− mice, while FcGRIIb−/− mice demonstrated the least tumor sizes compared with wild-type (WT). Intra-tumoral mononuclear cells of FcGRIIb−/− (hematoxylin and eosin staining) were more prominent than other groups with the most dominant CD86-positive cells (mostly M1 proinflammatory macrophages) and the least CD206-positive cells (mostly M2 anti-inflammatory macrophages). While fecal microbiome analysis demonstrated a subtle difference among mouse strains with tumors at 24 days post-cancer injection, serum cytokines (TNF-α, IL-6, IL-1α, IFN-β, IFN-γ, IL-23, IL-12p70, GM-CSF, IL-27, and IL-17A) (fluorescence-encoded bead multiplex assay) and the expansion of immune cells in the spleens of FcGRIIb−/− mice (flow cytometry) were more prominent than others. With bone marrow-derived macrophages, prominent M1 (LPS) and M2 polarization (IL4 and cancer supernatant) in FcGRIIb−/− and cGAS−/− macrophages, respectively, were demonstrated using polymerase chain reaction and flow cytometry. The most prominent tumoricidal activity (percentage of F4/80-negative flexible780 viable dye-positive cells using flow cytometry) of LPS-stimulated FcGRIIb−/− macrophages compared with other groups supported dominant pro-inflammatory characteristics of FcGRIIb−/− macrophages. Conclusions: In conclusion, the protective and promoting effects of FcGRIIb−/− and cGAS−/− mice, respectively, against cancers are partly related to macrophage functions with a subtle correlation to fecal microbiota, and FcGRIIb inhibitors and cGAS enhancers might be helpful for cancer adjuvant treatment.