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...

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Veröffentlicht in:Laboratory investigation 2024-12, Vol.104 (12), p.102159, Article 102159
Hauptverfasser: Ji, Saiyan, Fang, Huanying, Guan, Jingjie, He, Kun, Yang, Qingyuan
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Fang, Huanying
Guan, Jingjie
He, Kun
Yang, Qingyuan
description 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 (TCs), 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, 8 spatial interactions were identified, including 5 interactions between TC and CD20+ B sTILs, 2 interactions between CD3+ T sTILs and CD20+ B sTILs, and 1 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, to our knowledge, 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.
doi_str_mv 10.1016/j.labinv.2024.102159
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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 (TCs), 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, 8 spatial interactions were identified, including 5 interactions between TC and CD20+ B sTILs, 2 interactions between CD3+ T sTILs and CD20+ B sTILs, and 1 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, to our knowledge, our study is the first to provide in situ spatial immune characteristics at the proteomic level. 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Fang, Huanying ; Guan, Jingjie ; He, Kun ; Yang, Qingyuan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c241t-3233d7c43a74dfb4bb68fb41d73ebbe637237287fc5e192efb6ba3e81cd293473</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Aged</topic><topic>Biomarkers, Tumor - immunology</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>CD3 Complex - metabolism</topic><topic>colorectal cancer</topic><topic>Colorectal Neoplasms - immunology</topic><topic>Colorectal Neoplasms - metabolism</topic><topic>Female</topic><topic>GeoMx digital spatial profiling</topic><topic>Humans</topic><topic>immunoproteomics</topic><topic>immunoscore</topic><topic>intratumoral-infiltrating lymphocyte</topic><topic>Lymphocytes, Tumor-Infiltrating - immunology</topic><topic>Lymphocytes, Tumor-Infiltrating - metabolism</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Prognosis</topic><topic>Proteomics - methods</topic><topic>stromal-infiltrating lymphocyte</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ji, Saiyan</creatorcontrib><creatorcontrib>Fang, Huanying</creatorcontrib><creatorcontrib>Guan, Jingjie</creatorcontrib><creatorcontrib>He, Kun</creatorcontrib><creatorcontrib>Yang, Qingyuan</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Laboratory investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ji, Saiyan</au><au>Fang, Huanying</au><au>Guan, Jingjie</au><au>He, Kun</au><au>Yang, Qingyuan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Immunoproteomics Reveal Different Characteristics for the Prognostic Markers of Intratumoral-Infiltrating CD3+ T Lymphocytes and Immunoscore in Colorectal Cancer</atitle><jtitle>Laboratory investigation</jtitle><addtitle>Lab Invest</addtitle><date>2024-12</date><risdate>2024</risdate><volume>104</volume><issue>12</issue><spage>102159</spage><pages>102159-</pages><artnum>102159</artnum><issn>0023-6837</issn><issn>1530-0307</issn><eissn>1530-0307</eissn><abstract>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 (TCs), 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, 8 spatial interactions were identified, including 5 interactions between TC and CD20+ B sTILs, 2 interactions between CD3+ T sTILs and CD20+ B sTILs, and 1 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, to our knowledge, 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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>39419351</pmid><doi>10.1016/j.labinv.2024.102159</doi><orcidid>https://orcid.org/0000-0001-8808-1113</orcidid></addata></record>
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subjects Aged
Biomarkers, Tumor - immunology
Biomarkers, Tumor - metabolism
CD3 Complex - metabolism
colorectal cancer
Colorectal Neoplasms - immunology
Colorectal Neoplasms - metabolism
Female
GeoMx digital spatial profiling
Humans
immunoproteomics
immunoscore
intratumoral-infiltrating lymphocyte
Lymphocytes, Tumor-Infiltrating - immunology
Lymphocytes, Tumor-Infiltrating - metabolism
Male
Middle Aged
Prognosis
Proteomics - methods
stromal-infiltrating lymphocyte
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
title Immunoproteomics Reveal Different Characteristics for the Prognostic Markers of Intratumoral-Infiltrating CD3+ T Lymphocytes and Immunoscore in Colorectal Cancer
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