LBP3 promotes production of SCFAs to inhibit PMN-MDSC function and exert anti-tumor effects
10.3969/j.issn.1000-484X.2025.07.002
- VernacularTitle:LBP3促进SCFAs生成以抑制PMN-MDSC功能发挥抗肿瘤作用
- Author:
Yanping CAI
1
;
Meiling ZHANG
;
Xuting XIE
;
Junjie LIANG
;
Ying ZHU
;
Xiangliang DENG
;
Yunliang CHEN
;
Xia LUO
;
Lian ZHOU
;
Qing WANG
Author Information
1. 广州中医药大学中药学院,广州 510006
- Publication Type:Journal Article
- Keywords:
LBP3;
Polymorphonuclear-myeloid-derived suppressor cells;
Tumor immunity;
Short-chain fatty acid
- From:
Chinese Journal of Immunology
2025;41(7):1543-1551
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore whether LBP3 exerts anti-tumor effects by promoting production of short-chain fatty acids(SCFAs)by intestinal microbiota and regulating function of polymorphonuclear myeloid-derived suppressor cells(PMN-MDSC).Methods:A subcutaneous H22 liver cancer model was employed to assess anti-tumor activity of LBP3 and its regulatory effects on PMN-MDSC.Pseudo-sterile tumor-bearing mouse model was used to investigate role of intestinal microbiota in tumor suppression of LBP3.Fecal microbiota transplantation(FMT)was conducted to explore immune regulatory role of LBP3-modulated flora.Serum SCFAs levels in tumor-bearing mice were quantified using liquid chromatography-mass spectrometry,and effect of SCFAs butyrate on arginase 1(Arg-1)expression was evaluated in vitro.Results:Both low-dose(125 mg/kg)and high-dose(250 mg/kg)LBP3 signifi-cantly inhibited tumor growth in H22 tumor-bearing mice,also led to a marked reduction in proportion of PMN-MDSC in both spleen and tumor,a reduced proportion of Treg in lymphoid tissues,a decrease in Arg-1 level within tumor,infiltration of CD8+T cells into tumor was significantly enhanced.However,these effects of LBP3 were did not observed in pseudo-sterile mice,while the above changes could be reproduced after fecal supernatant transplantation in high-dose LBP3 treatment group,suggesting a crucial role for gut microbiota.Furthermore,co-expression of Ly6G and SCFA receptor GPR43 in tumor was also observed.LBP3 treatment resulted in increased levels of SCFAs,particularly butyrate,in both blood and tumor tissues.In vitro,butyrate was shown to inhibit Arg-1 expression in MSC-2 cells,further supporting hypothesis that SCFAs mediate immune-modulatory effects of LBP3.Conclusion:LBP3 exerts its anti-tumor effects by promoting SCFA production,which subsequently inhibits function of PMN-MDSC.This highlights LBP3's potential as an immunomodulatory agent in cancer therapy.
