AbstractMicrosatellite instability (MSI) is a phenotype characterized by changes in the sequence length of microsatellites in tumor cells and is closely linked to tumorigenesis and prognosis. Immune checkpoint inhibitors have shown good therapeutic effects in gastric cancer (GC) with MSI-high (MSI-H).

摘要微卫星不稳定性（MSI）是一种以肿瘤细胞中微卫星序列长度变化为特征的表型，与肿瘤发生和预后密切相关。免疫检查点抑制剂在MSI高（MSI-H）的胃癌（GC）中显示出良好的治疗效果。

However, the role of the novel immune checkpoint fibrinogen-like protein 1 (FGL1) in GC treatment has not been fully investigated. FGL1 expression in GC tissues and the difference in FGL1 immune infiltration between MSI/ microsatellite stability (MSS) patients were analyzed by bioinformatics and were verified in clinical samples.

然而，尚未充分研究新型免疫检查点纤维蛋白原样蛋白1（FGL1）在GC治疗中的作用。通过生物信息学分析了GC组织中FGL1的表达以及MSI/微卫星稳定性（MSS）患者之间FGL1免疫浸润的差异，并在临床样品中进行了验证。

Xenograft models of MSS and MSI GC were constructed in human immune reconstitution mice, and FGL1 expression in tumors was detected. Immunofluorescence and immunohistochemistry were used to assay the infiltration of immune cells in the two types of mice. Cytotoxicity and chemotaxis tests were used to detect the toxicity and chemotaxis of CD8+T cells to GC cells, respectively.

在人免疫重建小鼠中构建MSS和MSI GC的异种移植模型，并检测肿瘤中FGL1的表达。免疫荧光和免疫组织化学用于测定两种类型小鼠中免疫细胞的浸润。细胞毒性和趋化性试验分别用于检测CD8+T细胞对GC细胞的毒性和趋化性。

The cytokine content was detected by enzyme-linked immunosorbent assay. The therapeutic effects of FGL1 antibody on different types of GC were analyzed by xenograft mouse models. FGL1 exhibited significantly higher expression in GC, and its expression and immune cell infiltration levels were significantly higher in MSI GC than in MSS GC.

酶联免疫吸附试验检测细胞因子含量。通过异种移植小鼠模型分析FGL1抗体对不同类型GC的治疗效果。FGL1在GC中表现出显着更高的表达，并且其在MSI GC中的表达和免疫细胞浸润水平显着高于MSS GC。

CD8+T cells were significantly more effective in killing and chemotaxis of MSI GC cells than MSS GC cells. The FGL1 antibody was more effective in treating MSI GC.The novel immunosuppressor FGL1 antibody exerts a good therapeutic influence on MSI GC. These findings provide a basis for the development of drugs targeting FGL1 for MSI GC treatment..

CD8+T细胞在MSI GC细胞的杀伤和趋化性方面比MSS GC细胞更有效。FGL1抗体在治疗MSI GC方面更有效。新型免疫抑制剂FGL1抗体对MSI GC具有良好的治疗效果。这些发现为开发针对FGL1的MSI GC治疗药物提供了基础。。

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Fig. 1: FGL1 is highly expressed in MSI GC.Fig. 2: MSI GC has a higher level of immune cell infiltration.Fig. 3: FGL1 antibody inhibits immune escape in MSI GC.Fig. 4: MSI GC mice are more sensitive to anti-FGL1 treatment.

图1:FGL1在MSI GC中高度表达。。图3:FGL1抗体抑制MSI GC中的免疫逃逸。图4:MSI GC小鼠对抗FGL1治疗更敏感。

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The data used to support the findings of this study are available from the corresponding author upon request.

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Download referencesFundingThis research was supported by Natural Science Foundation of Zhejiang Province under grant number LY21H160053 and Hangzhou Medical College basic research key project under grant number KYZD2023011.Author informationAuthors and AffiliationsGeneral Surgery, Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, ChinaZhenyuan Qian, Jianzhang Wu, Kun Ke, Zaiyuan Ye & Fang WuZhejiang Chinese Medicine University, Hangzhou, Zhejiang, ChinaXufan CaiAuthorsZhenyuan QianView author publicationsYou can also search for this author in.

下载参考文献资助本研究得到了浙江省自然科学基金资助号LY21H160053和杭州医学院基础研究重点项目资助号KYZD203011的支持。作者信息作者和所属单位浙江省人民医院附属人民医院胃肠胰外科浙江省杭州医学院普通外科，浙江省杭州市钱振源，吴建章，柯坤，叶再元和方武浙江中医药大学，浙江杭州徐帆蔡作者钱振源观点作者出版物您也可以在中搜索这位作者。

PubMed Google ScholarXufan CaiView author publicationsYou can also search for this author in

PubMed Google ScholarXufan CaiView作者出版物您也可以在

PubMed Google ScholarJianzhang WuView author publicationsYou can also search for this author in

PubMed Google ScholarJianzhang WuView作者出版物您也可以在

PubMed Google ScholarKun KeView author publicationsYou can also search for this author in

PubMed Google ScholarKun KeView作者出版物您也可以在

PubMed Google ScholarZaiyuan YeView author publicationsYou can also search for this author in

PubMed Google ScholarZaiyuan YeView作者出版物您也可以在

PubMed Google ScholarFang WuView author publicationsYou can also search for this author in

PubMed Google ScholarFang WuView作者出版物您也可以在

PubMed Google ScholarContributionsZYQ conceived and designed the study. XFC, JZW, and KK performed the experiments and collected the data. ZYY analyzed and interpreted the data. FW contributed to the manuscript writing and editing. All authors read and approved the final manuscript.Corresponding authorsCorrespondence to.

PubMed Google ScholarContributionsZYQ构思并设计了这项研究。XFC，JZW和KK进行了实验并收集了数据。ZYY分析并解释了数据。。所有作者都阅读并批准了最终手稿。通讯作者通讯。

Zaiyuan Ye or Fang Wu.Ethics declarations

再圆叶或方武。道德宣言

Competing interests

相互竞争的利益

The authors declare no competing interests.

作者声明没有利益冲突。

Ethics approval and consent to participate

道德批准和同意参与

This study was approved by the Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital Ethics Committee with approval number 202403251133000525844. And obtained informed consent from the patient. All animals were kept in a pathogen-free environment and fed ad lib. The procedures for care and use of animals were approved by the Ethics Committee of Zhejiang Provincial People’s Hospital with approval number 20230419162308960584 and all applicable institutional and governmental regulations concerning the ethical use of animals were followed.

本研究经浙江省人民医院附属人民医院伦理委员会批准，批准号为202403251133000525844。并获得患者的知情同意。将所有动物保持在无病原体的环境中并随意喂养。动物护理和使用程序经浙江省人民医院伦理委员会批准，批准号为20230419162308960584，并遵循所有有关动物伦理使用的适用机构和政府法规。

All methods were performed in accordance with the relevant guidelines and regulations..

所有方法均按照相关指南和法规进行。。

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a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.Reprints and permissionsAbout this articleCite this articleQian, Z., Cai, X., Wu, J.

协会或其他合作伙伴）根据与作者或其他权利持有人的出版协议对本文拥有专有权；本文接受稿件版本的作者自行存档仅受此类出版协议和适用法律的条款管辖。转载和许可本文引用本文Qian，Z.，Cai，X.，Wu，J。

et al. FGL1 facilitates rather than suppresses anticancer immunity against microsatellite instable gastric cancer..

FGL1促进而不是抑制针对微卫星不稳定胃癌的抗癌免疫力。。

Genes Immun (2024). https://doi.org/10.1038/s41435-024-00314-2Download citationReceived: 27 November 2023Revised: 24 November 2024Accepted: 03 December 2024Published: 13 December 2024DOI: https://doi.org/10.1038/s41435-024-00314-2Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

基因免疫（2024）。https://doi.org/10.1038/s41435-024-00314-2Download引文接收日期：2023年11月27日修订日期：2024年11月24日接受日期：2024年12月3日发布日期：2024年12月13日OI：https://doi.org/10.1038/s41435-024-00314-2Share本文与您共享以下链接的任何人都可以阅读此内容：获取可共享链接对不起，本文目前没有可共享的链接。复制到剪贴板。

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