中国免疫学杂志2025，Vol.41Issue(7)：1543-1551,9.DOI:10.3969/j.issn.1000-484X.2025.07.002
LBP3促进SCFAs生成以抑制PMN-MDSC功能发挥抗肿瘤作用
LBP3 promotes production of SCFAs to inhibit PMN-MDSC function and exert anti-tumor effects
摘要
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.关键词
LBP3/多形核骨髓来源的抑制性细胞/肿瘤免疫/短链脂肪酸Key words
LBP3/Polymorphonuclear-myeloid-derived suppressor cells/Tumor immunity/Short-chain fatty acid分类
医药卫生引用本文复制引用
蔡燕萍,王青,张美玲,谢旭婷,梁俊杰,朱颖,邓向亮,陈允亮,罗霞,周联..LBP3促进SCFAs生成以抑制PMN-MDSC功能发挥抗肿瘤作用[J].中国免疫学杂志,2025,41(7):1543-1551,9.基金项目
国家自然科学基金面上项目(82474142,82074092). （82474142,82074092）
