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FGL1 Promotes Tumor Immune Escape in Stomach Adenocarcinoma via the Notch Signaling Pathway

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Abstract

Immune escape is the major reason for immunotherapy failure in stomach adenocarcinoma (STAD). We tried to reveal the underlying mechanism of FGL1 influencing STAD in this study. Bioinformatics analyses were conducted to analyze the expression of FGL1, the signaling pathways affected by FGL1, and the relation between FGL1 and immune cell infiltration. Quantitative real-time PCR (qRT-PCR), cell counting kit-8 assay, colony formation assay, flow cytometry and Transwell assay were adopted to analyze FGL1 expression, cell viability, cell proliferation, cell apoptosis, and cell invasion, respectively. Enzyme-linked immunosorbent assay, lactate dehydrogenase method, qRT-PCR and Western blot were adopted to reveal proinflammatory cytokine expression, cytotoxicity and mRNA and protein expression of the Notch signaling-related genes, respectively, after co-culture of STAD cells and CD8+T cells. Nude mice experiment was conducted to validate the results obtained above. FGL1 expressed highly in STAD and could activate the Notch signaling pathway, and it was negatively correlated with CD8+T cell infiltration. Cell experiments confirmed that high expression of FGL1 facilitated proliferation and hindered apoptosis of STAD cells. Knockdown of FGL1 could facilitate expression of pro-inflammatory factors and the cytotoxicity of CD8+T cells in co-culture system of STAD and CD8+ T cells. Knockdown of FGL1 could suppress the expression of the Notch signaling pathway-related genes, and the addition of Notch inhibitor proved that FGL1 promoted immune escape via the Notch signaling pathway. This study investigated the influence of FGL1 on STAD immune escape and demonstrated that FGL1 inhibited CD8+ T cell activation by activating the Notch signaling pathway and thus promoted tumor immune escape in STAD, providing a new potential diagnostic marker and therapeutic target for the immunotherapy of STAD patients.

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The data and materials in the current study are available from the corresponding author on reasonable request.

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Funding

This study was supported by The Natural Science Foundation of Shaanxi Province (2020JM-630); and Shangluo City Science and Technology Research and Development Plan Project (2020-Z-0061).

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Authors and Affiliations

  1. School of Health Management, Shangluo University, Shangluo, 726000, China

    Yani Zhou

  2. Department of Rheumatology, First Affiliated Hospital of Xi’an Medical College, Xi’an, 710077, China

    Dan Liu

  3. Department of Mathematics and Computer Application, Shangluo University, No. 10, Beixin Street, Shangzhou District, Shangluo, 726000, Shaanxi Province, China

    Huirong Li

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Contributions

YZ participated in the design and drafted the manuscript, DL conducted the experiments and revised it, HL collected and assembled the data. All authors read the article and approved submitted version.

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Correspondence to Huirong Li.

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The study was approved by the ethics committee of Shangluo University. The methods were carried out in accordance with the approved guidelines.

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Zhou, Y., Liu, D. & Li, H. FGL1 Promotes Tumor Immune Escape in Stomach Adenocarcinoma via the Notch Signaling Pathway. Mol Biotechnol (2023). https://doi.org/10.1007/s12033-023-00928-3

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