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Journal Of Modern Oncology[ISSN:1672-4992/CN:61-1415/R]

Issue:

2024 09

Page:

1573-1580

Research Field:

Publishing date:

Info

Title:

A preliminary investigation of the mechanism of the anti-lung adenocarcinoma effect of astragalus polysaccharide by modulating T cell sensitization of PD-L1 blockers

Author(s):

LIU Haizhao¹; JIN Yutong¹; ZHANG Ruixuan¹; HE Yi²; BIAN Yuhong¹

1.School of Integrative Medicine,Tianjin University of Traditional Chinese Medicine，Tianjin 301617,China；2.Department of Pharmacology,Institute of Basic Medical Sciences Chinese Academy of Medical Sciences and School of Basic Medicine Peking Union Medical College,Beijing 100005,China.

Keywords:

astragalus polysaccharide; PD-L1 blocker; lung adenocarcinoma; cytokines; tumor immune microenvironment

PACS:

R734.2

DOI:

10.3969/j.issn.1672-4992.2024.09.001

Abstract:

Objective：To observe the effect of astragalus polysaccharide combined with PD-L1 blocker on subcutaneous tumor growth in Lewis lung adenocarcinoma mice,and to preliminarily explore the possible mechanism of action of astragalus polysaccharide to promote the proliferation of T-cells based on the tumor immune microenvironment and to sensitize the PD-L1 blocker for the treatment of lung adenocarcinoma.Methods:Lewis lung adenocarcinoma mouse model was established,and after modeling,astragali polysaccharide combined with PD-L1 blocker was given to treat the tumor,while the two alone groups were set up separately.The tumor inhibition rate,spleen index and thymus index were calculated at the end of drug administration.HE staining was used to observe the pathological changes of tumor tissues.Flow cytometry was used to detect the ratio of CD4+ and CD8+ T cells in the peripheral blood.Immunofluorescence was used to detect the infiltration of T cells.The levels of the pro-inflammatory factors IL-1β,IL-6,and TNF-α were detected by ELISA in the tumor tissues.IL-10 and TGF-β protein expression in tumor tissues by Western Blot.Results:Compared with the model group,astragalus polysaccharide combined with PD-L1 blocker group could significantly increase the body weight of the loaded mice,reduce the tumor weight,up-regulate the splenic index and thymic index,and inhibit the tumor growth.At the same time,the astragalus polysaccharide combined with PD-L1 blocker group could significantly increase the ratio of CD4+ T cells(CD3+CD4+) and the ratio of CD4+ /CD8+ T cells(CD3+CD4+/ CD3+CD8+) ratio,enhanced the infiltration of CD4+ and CD8+ T cells in tumor tissues,promoted the secretion of pro-inflammatory cytokines IL-1β,IL-6,and TNF-α,and decreased the expression of immunosuppressive factors IL-10 and TGF-β in tumor tissues of mice.Conclusion:Astragali polysaccharide combined with PD-L1 blocker has a better anti-tumor effect on Lewis lung adenocarcinoma mice.Astragali polysaccharide can exert the anti-tumor effect of sensitizing PD-L1 blocker against lung adenocarcinoma by improving the immune microenvironment of the tumors,and increasing the infiltration of T-cells in the tumor tissues.

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Memo

Memo:

National Natural Science Foundation of China（No.82374320,81573707）;国家自然科学基金资助项目（编号：82374320,81573707）；天津中医药大学研究生科研创新项目(编号：YJSKC-20231005);天津中医药大学中西医结合学院研究生创新基金项目（编号：ZXYCXLX202206）

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Last Update: 2024-03-29