免疫蛋白组学揭示了结直肠癌瘤内浸润 CD3+ T 淋巴细胞和免疫镜检的预后标志物的不同特征。

IF 5.1 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL Laboratory Investigation Pub Date : 2024-10-15 DOI:10.1016/j.labinv.2024.102159
Saiyan Ji, Huanying Fang, Jingjie Guan, Kun He, Qingyuan Yang
{"title":"免疫蛋白组学揭示了结直肠癌瘤内浸润 CD3+ T 淋巴细胞和免疫镜检的预后标志物的不同特征。","authors":"Saiyan Ji, Huanying Fang, Jingjie Guan, Kun He, Qingyuan Yang","doi":"10.1016/j.labinv.2024.102159","DOIUrl":null,"url":null,"abstract":"<p><p>Tumor-infiltrating lymphocytes (TILs) and immunoscoring based on densities of CD3+ and CD8+ TILs are both favorable prognostic markers in colorectal cancer (CRC). However, determination of the molecular features of TILs, particularly their immunoproteomic signatures would require the development of large-scale in situ spatiotemporal technologies. Recently, a multiplex in situ digital spatial proteomic profiling (DSP) tool GeoMx DSP has been applied to identify biomarkers predictive of therapeutic responses and to understand disease mechanisms and progression. Taking advantage of this tool, we simultaneously characterized the spatial distribution and interactions of 42 immune proteins in tumor cells (TC), CD3+ T stromal TILs (sTILs), and CD20+ B sTILs using tissue microarrays, and further studied their associations with CD3+ T TILs and immunoscores in CRC. First, our data showed that well-known immune checkpoints, such as PD-L1, PD-L2, and LAG3, were expressed at low levels, whereas some other immune proteins, such as CD11c, CD68, STING, and CD44, were highly expressed. Second, eight spatial interactions were identified, including five interactions between TC and CD20+ B sTILs, two interactions between CD3+ T sTILs and CD20+ B sTILs, and one interaction among TC, CD3+ T sTILs, and CD20+ B sTILs. Third, the differential immune microlandscape in the spatial compartments was identified in tissues with positive CD3+ T intratumoral TILs and high immunoscores. Collectively, our study is the first to provide in situ spatial immune characteristics at the proteomic level. Moreover, our findings provide direct evidence supporting the infiltration of CD3+ T sTILs from stoma to TC and shed important insights into better understanding and treating CRC patients related to different immune prognostic markers.</p>","PeriodicalId":17930,"journal":{"name":"Laboratory Investigation","volume":null,"pages":null},"PeriodicalIF":5.1000,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Immunoproteomics reveal different characteristics for the prognostic markers of intratumoral-infiltrating CD3+ T lymphocytes and immunoscore in colorectal cancer.\",\"authors\":\"Saiyan Ji, Huanying Fang, Jingjie Guan, Kun He, Qingyuan Yang\",\"doi\":\"10.1016/j.labinv.2024.102159\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Tumor-infiltrating lymphocytes (TILs) and immunoscoring based on densities of CD3+ and CD8+ TILs are both favorable prognostic markers in colorectal cancer (CRC). However, determination of the molecular features of TILs, particularly their immunoproteomic signatures would require the development of large-scale in situ spatiotemporal technologies. Recently, a multiplex in situ digital spatial proteomic profiling (DSP) tool GeoMx DSP has been applied to identify biomarkers predictive of therapeutic responses and to understand disease mechanisms and progression. Taking advantage of this tool, we simultaneously characterized the spatial distribution and interactions of 42 immune proteins in tumor cells (TC), CD3+ T stromal TILs (sTILs), and CD20+ B sTILs using tissue microarrays, and further studied their associations with CD3+ T TILs and immunoscores in CRC. First, our data showed that well-known immune checkpoints, such as PD-L1, PD-L2, and LAG3, were expressed at low levels, whereas some other immune proteins, such as CD11c, CD68, STING, and CD44, were highly expressed. Second, eight spatial interactions were identified, including five interactions between TC and CD20+ B sTILs, two interactions between CD3+ T sTILs and CD20+ B sTILs, and one interaction among TC, CD3+ T sTILs, and CD20+ B sTILs. Third, the differential immune microlandscape in the spatial compartments was identified in tissues with positive CD3+ T intratumoral TILs and high immunoscores. Collectively, our study is the first to provide in situ spatial immune characteristics at the proteomic level. Moreover, our findings provide direct evidence supporting the infiltration of CD3+ T sTILs from stoma to TC and shed important insights into better understanding and treating CRC patients related to different immune prognostic markers.</p>\",\"PeriodicalId\":17930,\"journal\":{\"name\":\"Laboratory Investigation\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2024-10-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Laboratory Investigation\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.labinv.2024.102159\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Laboratory Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.labinv.2024.102159","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

摘要

肿瘤浸润淋巴细胞(TILs)和基于 CD3+ 和 CD8+ TILs 密度的免疫镜检都是结直肠癌(CRC)的有利预后指标。然而,要确定TILs的分子特征,特别是其免疫蛋白组学特征,需要开发大规模的原位时空技术。最近,一种多重原位数字空间蛋白质组剖析(DSP)工具GeoMx DSP已被应用于确定预测治疗反应的生物标记物,并了解疾病的机制和进展。利用这一工具,我们使用组织芯片同时鉴定了肿瘤细胞(TC)、CD3+ T基质TILs(sTILs)和CD20+ B sTILs中42种免疫蛋白的空间分布和相互作用,并进一步研究了它们与CRC中CD3+ T TILs和免疫标志物的关联。首先,我们的数据显示,PD-L1、PD-L2 和 LAG3 等知名免疫检查点的表达水平较低,而 CD11c、CD68、STING 和 CD44 等其他免疫蛋白的表达水平较高。第二,发现了八种空间相互作用,包括五种 TC 与 CD20+ B sTILs 之间的相互作用,两种 CD3+ T sTILs 与 CD20+ B sTILs 之间的相互作用,以及一种 TC、CD3+ T sTILs 和 CD20+ B sTILs 之间的相互作用。第三,在瘤内 CD3+ T TILs 阳性且免疫分数较高的组织中发现了空间分区中不同的免疫微景观。总之,我们的研究首次在蛋白质组水平上提供了原位空间免疫特征。此外,我们的研究结果为 CD3+ T sTILs 从造口向 TC 的浸润提供了直接证据,并为更好地理解和治疗与不同免疫预后标志物相关的 CRC 患者提供了重要启示。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
Immunoproteomics reveal different characteristics for the prognostic markers of intratumoral-infiltrating CD3+ T lymphocytes and immunoscore in colorectal cancer.

Tumor-infiltrating lymphocytes (TILs) and immunoscoring based on densities of CD3+ and CD8+ TILs are both favorable prognostic markers in colorectal cancer (CRC). However, determination of the molecular features of TILs, particularly their immunoproteomic signatures would require the development of large-scale in situ spatiotemporal technologies. Recently, a multiplex in situ digital spatial proteomic profiling (DSP) tool GeoMx DSP has been applied to identify biomarkers predictive of therapeutic responses and to understand disease mechanisms and progression. Taking advantage of this tool, we simultaneously characterized the spatial distribution and interactions of 42 immune proteins in tumor cells (TC), CD3+ T stromal TILs (sTILs), and CD20+ B sTILs using tissue microarrays, and further studied their associations with CD3+ T TILs and immunoscores in CRC. First, our data showed that well-known immune checkpoints, such as PD-L1, PD-L2, and LAG3, were expressed at low levels, whereas some other immune proteins, such as CD11c, CD68, STING, and CD44, were highly expressed. Second, eight spatial interactions were identified, including five interactions between TC and CD20+ B sTILs, two interactions between CD3+ T sTILs and CD20+ B sTILs, and one interaction among TC, CD3+ T sTILs, and CD20+ B sTILs. Third, the differential immune microlandscape in the spatial compartments was identified in tissues with positive CD3+ T intratumoral TILs and high immunoscores. Collectively, our study is the first to provide in situ spatial immune characteristics at the proteomic level. Moreover, our findings provide direct evidence supporting the infiltration of CD3+ T sTILs from stoma to TC and shed important insights into better understanding and treating CRC patients related to different immune prognostic markers.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Laboratory Investigation
Laboratory Investigation 医学-病理学
CiteScore
8.30
自引率
0.00%
发文量
125
审稿时长
2 months
期刊介绍: Laboratory Investigation is an international journal owned by the United States and Canadian Academy of Pathology. Laboratory Investigation offers prompt publication of high-quality original research in all biomedical disciplines relating to the understanding of human disease and the application of new methods to the diagnosis of disease. Both human and experimental studies are welcome.
期刊最新文献
Deciphering the intricate relationship between macrophages, pigmentation, and prognosis in uveal melanoma. Leptin modulates ovarian granulosa cell apoptosis by regulating telomerase activity and telomere length in polycystic ovary syndrome. Epigenomic and Transcriptomic Profiling of Solitary Fibrous Tumors Identifies Site-Specific Patterns and Candidate Genes Regulated by DNA Methylation Nup210 Promotes Colorectal Cancer Progression by Regulating Nuclear Plasma Transport Highly-Multiplexed Immunofluorescence PhenoCycler Panel for Murine FFPE Yields Insight into Tumor Microenvironment Immunoengineering.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1