High PTX3 expression is associated with a poor prognosis in diffuse large B‐cell lymphoma
Tumor‐associated macrophages (TAMs) are associated with a poor prognosis of diffuse large B‐cell lymphoma (DLBCL). As macrophages are heterogeneous, the immune polarization and their pathological role warrant further study. We characterized the microenvironment of DLBCL by immunohistochemistry in a...
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| Veröffentlicht in: | Cancer science 2022-01, Vol.113 (1), p.334-348 |
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| creator | Carreras, Joaquim Kikuti, Yara Yukie Hiraiwa, Shinichiro Miyaoka, Masashi Tomita, Sakura Ikoma, Haruka Ito, Atsushi Kondo, Yusuke Itoh, Johbu Roncador, Giovanna Martinez, Antonio Colomo, Lluis Hamoudi, Rifat Ando, Kiyoshi Nakamura, Naoya |
| description | Tumor‐associated macrophages (TAMs) are associated with a poor prognosis of diffuse large B‐cell lymphoma (DLBCL). As macrophages are heterogeneous, the immune polarization and their pathological role warrant further study. We characterized the microenvironment of DLBCL by immunohistochemistry in a training set of 132 cases, which included 10 Epstein–Barr virus‐encoded small RNA (EBER)‐positive and five high‐grade B‐cell lymphomas, with gene expression profiling in a representative subset of 37 cases. Diffuse large B‐cell lymphoma had a differential infiltration of TAMs. The high infiltration of CD68 (pan‐macrophages), CD16 (M1‐like), CD163, pentraxin 3 (PTX3), and interleukin (IL)‐10‐positive macrophages (M2c‐like) and low infiltration of FOXP3‐positive regulatory T lymphocytes (Tregs) correlated with poor survival. Activated B cell‐like DLBCL was associated with high CD16, CD163, PTX3, and IL‐10, and EBER‐positive DLBCL with high CD163 and PTX3. Programmed cell death‐ligand 1 positively correlated with CD16, CD163, IL‐10, and RGS1. In a multivariate analysis of overall survival, PTX3 and International Prognostic Index were identified as the most relevant variables. The gene expression analysis showed upregulation of genes involved in innate and adaptive immune responses and macrophage and Toll‐like receptor pathways in high PTX3 cases. The prognostic relevance of PTX3 was confirmed in a validation set of 159 cases. Finally, in a series from Europe and North America (GSE10846, R‐CHOP‐like treatment, n = 233) high gene expression of PTX3 correlated with poor survival, and moderately with CSF1R, CD16, MITF, CD163, MYC, and RGS1. Therefore, the high infiltration of M2c‐like immune regulatory macrophages and low infiltration of FOXP3‐positive Tregs is associated with a poor prognosis in DLBCL, for which PTX3 is a new prognostic biomarker.
This research focused on the analysis of several macrophage and regulatory T lymphocyte markers in diffuse large b‐cell lymphoma. We found that high PTX3 expression correlated with poor prognosis of the patients. |
| doi_str_mv | 10.1111/cas.15179 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8748251</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2618379925</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4679-c52328724bc782567a58f9be7bf59d6c97dcb3f713d27ce84ef48fb0be833f413</originalsourceid><addsrcrecordid>eNp1kc1KHTEUx0NpqVa78AVKoJt2MZqvycemYC-tFoQKKghdhEwmuTcyM5kmd2rvro_gM_ok5nqt2ILZJJz8-J1z-AOwh9E-LufAmryPayzUC7CNKVOVQIi_vH-LSiFKtsCbnK8Qopwp9hpslTrimPBt8OM4zBfw9PySQvd7TC7nEAcYMjQ5RxvM0rXwOiwX0MAxxgTHFOdDzAUIA2yD91N2sDNp7uDn2z831nUd7Fb9uIi92QWvvOmye_tw74CLr1_OZ8fVyfejb7PDk8oyLlRla0KJFIQ1VkhSc2Fq6VXjRONr1XKrRGsb6gWmLRHWSeY8k75BjZOUeobpDvi08Y5T07vWumGZTKfHFHqTVjqaoP_9GcJCz-MvLQUrDdeCDw-CFH9OLi91H_J6FTO4OGVNailEzakQBX3_H3oVpzSU9TThWFKhFKkL9XFD2RRzTs4_DoORXkemS2T6PrLCvns6_SP5N6MCHGyA69C51fMmPTs82yjvAOqKobE</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2618379925</pqid></control><display><type>article</type><title>High PTX3 expression is associated with a poor prognosis in diffuse large B‐cell lymphoma</title><source>MEDLINE</source><source>Wiley Online Library Open Access</source><source>DOAJ Directory of Open Access Journals</source><source>Wiley Online Library Journals Frontfile Complete</source><source>PubMed Central</source><creator>Carreras, Joaquim ; Kikuti, Yara Yukie ; Hiraiwa, Shinichiro ; Miyaoka, Masashi ; Tomita, Sakura ; Ikoma, Haruka ; Ito, Atsushi ; Kondo, Yusuke ; Itoh, Johbu ; Roncador, Giovanna ; Martinez, Antonio ; Colomo, Lluis ; Hamoudi, Rifat ; Ando, Kiyoshi ; Nakamura, Naoya</creator><creatorcontrib>Carreras, Joaquim ; Kikuti, Yara Yukie ; Hiraiwa, Shinichiro ; Miyaoka, Masashi ; Tomita, Sakura ; Ikoma, Haruka ; Ito, Atsushi ; Kondo, Yusuke ; Itoh, Johbu ; Roncador, Giovanna ; Martinez, Antonio ; Colomo, Lluis ; Hamoudi, Rifat ; Ando, Kiyoshi ; Nakamura, Naoya</creatorcontrib><description>Tumor‐associated macrophages (TAMs) are associated with a poor prognosis of diffuse large B‐cell lymphoma (DLBCL). As macrophages are heterogeneous, the immune polarization and their pathological role warrant further study. We characterized the microenvironment of DLBCL by immunohistochemistry in a training set of 132 cases, which included 10 Epstein–Barr virus‐encoded small RNA (EBER)‐positive and five high‐grade B‐cell lymphomas, with gene expression profiling in a representative subset of 37 cases. Diffuse large B‐cell lymphoma had a differential infiltration of TAMs. The high infiltration of CD68 (pan‐macrophages), CD16 (M1‐like), CD163, pentraxin 3 (PTX3), and interleukin (IL)‐10‐positive macrophages (M2c‐like) and low infiltration of FOXP3‐positive regulatory T lymphocytes (Tregs) correlated with poor survival. Activated B cell‐like DLBCL was associated with high CD16, CD163, PTX3, and IL‐10, and EBER‐positive DLBCL with high CD163 and PTX3. Programmed cell death‐ligand 1 positively correlated with CD16, CD163, IL‐10, and RGS1. In a multivariate analysis of overall survival, PTX3 and International Prognostic Index were identified as the most relevant variables. The gene expression analysis showed upregulation of genes involved in innate and adaptive immune responses and macrophage and Toll‐like receptor pathways in high PTX3 cases. The prognostic relevance of PTX3 was confirmed in a validation set of 159 cases. Finally, in a series from Europe and North America (GSE10846, R‐CHOP‐like treatment, n = 233) high gene expression of PTX3 correlated with poor survival, and moderately with CSF1R, CD16, MITF, CD163, MYC, and RGS1. Therefore, the high infiltration of M2c‐like immune regulatory macrophages and low infiltration of FOXP3‐positive Tregs is associated with a poor prognosis in DLBCL, for which PTX3 is a new prognostic biomarker.
This research focused on the analysis of several macrophage and regulatory T lymphocyte markers in diffuse large b‐cell lymphoma. We found that high PTX3 expression correlated with poor prognosis of the patients.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.15179</identifier><identifier>PMID: 34706126</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Adaptive Immunity ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Apoptosis ; B-cell lymphoma ; C-Reactive Protein - genetics ; CD16 antigen ; CD163 antigen ; Cell death ; Cell survival ; Cytokines ; Dehydrogenases ; diffuse large B‐cell lymphoma ; Epstein-Barr virus ; Epstein-Barr Virus Infections - genetics ; Epstein-Barr Virus Infections - immunology ; Female ; Foxp3 protein ; Gene expression ; Gene Expression Regulation, Neoplastic ; Herpesvirus 4, Human - genetics ; Humans ; IL‐10 ; Immunity, Innate ; Immunohistochemistry ; Infiltration ; Ligands ; Lymphocytes T ; Lymphoma ; Lymphoma, Large B-Cell, Diffuse - genetics ; Lymphoma, Large B-Cell, Diffuse - immunology ; Lymphoma, Large B-Cell, Diffuse - virology ; Macrophages ; Male ; Medical prognosis ; Metastases ; Microenvironments ; Middle Aged ; Multivariate analysis ; Myc protein ; Original ; Pathogenesis ; PD‐L1, CD163 ; Pentraxins ; Prognosis ; Proteins ; PTX3 ; RNA viruses ; RNA, Viral - genetics ; Serum Amyloid P-Component - genetics ; Survival Analysis ; Tumor Microenvironment ; Tumor necrosis factor-TNF ; Tumor-Associated Macrophages - immunology ; Tumors ; Up-Regulation ; Young Adult</subject><ispartof>Cancer science, 2022-01, Vol.113 (1), p.334-348</ispartof><rights>2021 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2021 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2022. This work is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4679-c52328724bc782567a58f9be7bf59d6c97dcb3f713d27ce84ef48fb0be833f413</citedby><cites>FETCH-LOGICAL-c4679-c52328724bc782567a58f9be7bf59d6c97dcb3f713d27ce84ef48fb0be833f413</cites><orcidid>0000-0002-1402-0868 ; 0000-0003-3358-5845 ; 0000-0002-0650-7609 ; 0000-0003-0790-9017 ; 0000-0003-4332-5254 ; 0000-0002-6129-8299 ; 0000-0001-5236-5085 ; 0000-0002-9807-2875</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748251/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8748251/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34706126$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carreras, Joaquim</creatorcontrib><creatorcontrib>Kikuti, Yara Yukie</creatorcontrib><creatorcontrib>Hiraiwa, Shinichiro</creatorcontrib><creatorcontrib>Miyaoka, Masashi</creatorcontrib><creatorcontrib>Tomita, Sakura</creatorcontrib><creatorcontrib>Ikoma, Haruka</creatorcontrib><creatorcontrib>Ito, Atsushi</creatorcontrib><creatorcontrib>Kondo, Yusuke</creatorcontrib><creatorcontrib>Itoh, Johbu</creatorcontrib><creatorcontrib>Roncador, Giovanna</creatorcontrib><creatorcontrib>Martinez, Antonio</creatorcontrib><creatorcontrib>Colomo, Lluis</creatorcontrib><creatorcontrib>Hamoudi, Rifat</creatorcontrib><creatorcontrib>Ando, Kiyoshi</creatorcontrib><creatorcontrib>Nakamura, Naoya</creatorcontrib><title>High PTX3 expression is associated with a poor prognosis in diffuse large B‐cell lymphoma</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>Tumor‐associated macrophages (TAMs) are associated with a poor prognosis of diffuse large B‐cell lymphoma (DLBCL). As macrophages are heterogeneous, the immune polarization and their pathological role warrant further study. We characterized the microenvironment of DLBCL by immunohistochemistry in a training set of 132 cases, which included 10 Epstein–Barr virus‐encoded small RNA (EBER)‐positive and five high‐grade B‐cell lymphomas, with gene expression profiling in a representative subset of 37 cases. Diffuse large B‐cell lymphoma had a differential infiltration of TAMs. The high infiltration of CD68 (pan‐macrophages), CD16 (M1‐like), CD163, pentraxin 3 (PTX3), and interleukin (IL)‐10‐positive macrophages (M2c‐like) and low infiltration of FOXP3‐positive regulatory T lymphocytes (Tregs) correlated with poor survival. Activated B cell‐like DLBCL was associated with high CD16, CD163, PTX3, and IL‐10, and EBER‐positive DLBCL with high CD163 and PTX3. Programmed cell death‐ligand 1 positively correlated with CD16, CD163, IL‐10, and RGS1. In a multivariate analysis of overall survival, PTX3 and International Prognostic Index were identified as the most relevant variables. The gene expression analysis showed upregulation of genes involved in innate and adaptive immune responses and macrophage and Toll‐like receptor pathways in high PTX3 cases. The prognostic relevance of PTX3 was confirmed in a validation set of 159 cases. Finally, in a series from Europe and North America (GSE10846, R‐CHOP‐like treatment, n = 233) high gene expression of PTX3 correlated with poor survival, and moderately with CSF1R, CD16, MITF, CD163, MYC, and RGS1. Therefore, the high infiltration of M2c‐like immune regulatory macrophages and low infiltration of FOXP3‐positive Tregs is associated with a poor prognosis in DLBCL, for which PTX3 is a new prognostic biomarker.
This research focused on the analysis of several macrophage and regulatory T lymphocyte markers in diffuse large b‐cell lymphoma. We found that high PTX3 expression correlated with poor prognosis of the patients.</description><subject>Adaptive Immunity</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Apoptosis</subject><subject>B-cell lymphoma</subject><subject>C-Reactive Protein - genetics</subject><subject>CD16 antigen</subject><subject>CD163 antigen</subject><subject>Cell death</subject><subject>Cell survival</subject><subject>Cytokines</subject><subject>Dehydrogenases</subject><subject>diffuse large B‐cell lymphoma</subject><subject>Epstein-Barr virus</subject><subject>Epstein-Barr Virus Infections - genetics</subject><subject>Epstein-Barr Virus Infections - immunology</subject><subject>Female</subject><subject>Foxp3 protein</subject><subject>Gene expression</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Herpesvirus 4, Human - genetics</subject><subject>Humans</subject><subject>IL‐10</subject><subject>Immunity, Innate</subject><subject>Immunohistochemistry</subject><subject>Infiltration</subject><subject>Ligands</subject><subject>Lymphocytes T</subject><subject>Lymphoma</subject><subject>Lymphoma, Large B-Cell, Diffuse - genetics</subject><subject>Lymphoma, Large B-Cell, Diffuse - immunology</subject><subject>Lymphoma, Large B-Cell, Diffuse - virology</subject><subject>Macrophages</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Metastases</subject><subject>Microenvironments</subject><subject>Middle Aged</subject><subject>Multivariate analysis</subject><subject>Myc protein</subject><subject>Original</subject><subject>Pathogenesis</subject><subject>PD‐L1, CD163</subject><subject>Pentraxins</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>PTX3</subject><subject>RNA viruses</subject><subject>RNA, Viral - genetics</subject><subject>Serum Amyloid P-Component - genetics</subject><subject>Survival Analysis</subject><subject>Tumor Microenvironment</subject><subject>Tumor necrosis factor-TNF</subject><subject>Tumor-Associated Macrophages - immunology</subject><subject>Tumors</subject><subject>Up-Regulation</subject><subject>Young Adult</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp1kc1KHTEUx0NpqVa78AVKoJt2MZqvycemYC-tFoQKKghdhEwmuTcyM5kmd2rvro_gM_ok5nqt2ILZJJz8-J1z-AOwh9E-LufAmryPayzUC7CNKVOVQIi_vH-LSiFKtsCbnK8Qopwp9hpslTrimPBt8OM4zBfw9PySQvd7TC7nEAcYMjQ5RxvM0rXwOiwX0MAxxgTHFOdDzAUIA2yD91N2sDNp7uDn2z831nUd7Fb9uIi92QWvvOmye_tw74CLr1_OZ8fVyfejb7PDk8oyLlRla0KJFIQ1VkhSc2Fq6VXjRONr1XKrRGsb6gWmLRHWSeY8k75BjZOUeobpDvi08Y5T07vWumGZTKfHFHqTVjqaoP_9GcJCz-MvLQUrDdeCDw-CFH9OLi91H_J6FTO4OGVNailEzakQBX3_H3oVpzSU9TThWFKhFKkL9XFD2RRzTs4_DoORXkemS2T6PrLCvns6_SP5N6MCHGyA69C51fMmPTs82yjvAOqKobE</recordid><startdate>202201</startdate><enddate>202201</enddate><creator>Carreras, Joaquim</creator><creator>Kikuti, Yara Yukie</creator><creator>Hiraiwa, Shinichiro</creator><creator>Miyaoka, Masashi</creator><creator>Tomita, Sakura</creator><creator>Ikoma, Haruka</creator><creator>Ito, Atsushi</creator><creator>Kondo, Yusuke</creator><creator>Itoh, Johbu</creator><creator>Roncador, Giovanna</creator><creator>Martinez, Antonio</creator><creator>Colomo, Lluis</creator><creator>Hamoudi, Rifat</creator><creator>Ando, Kiyoshi</creator><creator>Nakamura, Naoya</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1402-0868</orcidid><orcidid>https://orcid.org/0000-0003-3358-5845</orcidid><orcidid>https://orcid.org/0000-0002-0650-7609</orcidid><orcidid>https://orcid.org/0000-0003-0790-9017</orcidid><orcidid>https://orcid.org/0000-0003-4332-5254</orcidid><orcidid>https://orcid.org/0000-0002-6129-8299</orcidid><orcidid>https://orcid.org/0000-0001-5236-5085</orcidid><orcidid>https://orcid.org/0000-0002-9807-2875</orcidid></search><sort><creationdate>202201</creationdate><title>High PTX3 expression is associated with a poor prognosis in diffuse large B‐cell lymphoma</title><author>Carreras, Joaquim ; Kikuti, Yara Yukie ; Hiraiwa, Shinichiro ; Miyaoka, Masashi ; Tomita, Sakura ; Ikoma, Haruka ; Ito, Atsushi ; Kondo, Yusuke ; Itoh, Johbu ; Roncador, Giovanna ; Martinez, Antonio ; Colomo, Lluis ; Hamoudi, Rifat ; Ando, Kiyoshi ; Nakamura, Naoya</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4679-c52328724bc782567a58f9be7bf59d6c97dcb3f713d27ce84ef48fb0be833f413</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adaptive Immunity</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Apoptosis</topic><topic>B-cell lymphoma</topic><topic>C-Reactive Protein - genetics</topic><topic>CD16 antigen</topic><topic>CD163 antigen</topic><topic>Cell death</topic><topic>Cell survival</topic><topic>Cytokines</topic><topic>Dehydrogenases</topic><topic>diffuse large B‐cell lymphoma</topic><topic>Epstein-Barr virus</topic><topic>Epstein-Barr Virus Infections - genetics</topic><topic>Epstein-Barr Virus Infections - immunology</topic><topic>Female</topic><topic>Foxp3 protein</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Herpesvirus 4, Human - genetics</topic><topic>Humans</topic><topic>IL‐10</topic><topic>Immunity, Innate</topic><topic>Immunohistochemistry</topic><topic>Infiltration</topic><topic>Ligands</topic><topic>Lymphocytes T</topic><topic>Lymphoma</topic><topic>Lymphoma, Large B-Cell, Diffuse - genetics</topic><topic>Lymphoma, Large B-Cell, Diffuse - immunology</topic><topic>Lymphoma, Large B-Cell, Diffuse - virology</topic><topic>Macrophages</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Metastases</topic><topic>Microenvironments</topic><topic>Middle Aged</topic><topic>Multivariate analysis</topic><topic>Myc protein</topic><topic>Original</topic><topic>Pathogenesis</topic><topic>PD‐L1, CD163</topic><topic>Pentraxins</topic><topic>Prognosis</topic><topic>Proteins</topic><topic>PTX3</topic><topic>RNA viruses</topic><topic>RNA, Viral - genetics</topic><topic>Serum Amyloid P-Component - genetics</topic><topic>Survival Analysis</topic><topic>Tumor Microenvironment</topic><topic>Tumor necrosis factor-TNF</topic><topic>Tumor-Associated Macrophages - immunology</topic><topic>Tumors</topic><topic>Up-Regulation</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carreras, Joaquim</creatorcontrib><creatorcontrib>Kikuti, Yara Yukie</creatorcontrib><creatorcontrib>Hiraiwa, Shinichiro</creatorcontrib><creatorcontrib>Miyaoka, Masashi</creatorcontrib><creatorcontrib>Tomita, Sakura</creatorcontrib><creatorcontrib>Ikoma, Haruka</creatorcontrib><creatorcontrib>Ito, Atsushi</creatorcontrib><creatorcontrib>Kondo, Yusuke</creatorcontrib><creatorcontrib>Itoh, Johbu</creatorcontrib><creatorcontrib>Roncador, Giovanna</creatorcontrib><creatorcontrib>Martinez, Antonio</creatorcontrib><creatorcontrib>Colomo, Lluis</creatorcontrib><creatorcontrib>Hamoudi, Rifat</creatorcontrib><creatorcontrib>Ando, Kiyoshi</creatorcontrib><creatorcontrib>Nakamura, Naoya</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carreras, Joaquim</au><au>Kikuti, Yara Yukie</au><au>Hiraiwa, Shinichiro</au><au>Miyaoka, Masashi</au><au>Tomita, Sakura</au><au>Ikoma, Haruka</au><au>Ito, Atsushi</au><au>Kondo, Yusuke</au><au>Itoh, Johbu</au><au>Roncador, Giovanna</au><au>Martinez, Antonio</au><au>Colomo, Lluis</au><au>Hamoudi, Rifat</au><au>Ando, Kiyoshi</au><au>Nakamura, Naoya</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High PTX3 expression is associated with a poor prognosis in diffuse large B‐cell lymphoma</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2022-01</date><risdate>2022</risdate><volume>113</volume><issue>1</issue><spage>334</spage><epage>348</epage><pages>334-348</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>Tumor‐associated macrophages (TAMs) are associated with a poor prognosis of diffuse large B‐cell lymphoma (DLBCL). As macrophages are heterogeneous, the immune polarization and their pathological role warrant further study. We characterized the microenvironment of DLBCL by immunohistochemistry in a training set of 132 cases, which included 10 Epstein–Barr virus‐encoded small RNA (EBER)‐positive and five high‐grade B‐cell lymphomas, with gene expression profiling in a representative subset of 37 cases. Diffuse large B‐cell lymphoma had a differential infiltration of TAMs. The high infiltration of CD68 (pan‐macrophages), CD16 (M1‐like), CD163, pentraxin 3 (PTX3), and interleukin (IL)‐10‐positive macrophages (M2c‐like) and low infiltration of FOXP3‐positive regulatory T lymphocytes (Tregs) correlated with poor survival. Activated B cell‐like DLBCL was associated with high CD16, CD163, PTX3, and IL‐10, and EBER‐positive DLBCL with high CD163 and PTX3. Programmed cell death‐ligand 1 positively correlated with CD16, CD163, IL‐10, and RGS1. In a multivariate analysis of overall survival, PTX3 and International Prognostic Index were identified as the most relevant variables. The gene expression analysis showed upregulation of genes involved in innate and adaptive immune responses and macrophage and Toll‐like receptor pathways in high PTX3 cases. The prognostic relevance of PTX3 was confirmed in a validation set of 159 cases. Finally, in a series from Europe and North America (GSE10846, R‐CHOP‐like treatment, n = 233) high gene expression of PTX3 correlated with poor survival, and moderately with CSF1R, CD16, MITF, CD163, MYC, and RGS1. Therefore, the high infiltration of M2c‐like immune regulatory macrophages and low infiltration of FOXP3‐positive Tregs is associated with a poor prognosis in DLBCL, for which PTX3 is a new prognostic biomarker.
This research focused on the analysis of several macrophage and regulatory T lymphocyte markers in diffuse large b‐cell lymphoma. We found that high PTX3 expression correlated with poor prognosis of the patients.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>34706126</pmid><doi>10.1111/cas.15179</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-1402-0868</orcidid><orcidid>https://orcid.org/0000-0003-3358-5845</orcidid><orcidid>https://orcid.org/0000-0002-0650-7609</orcidid><orcidid>https://orcid.org/0000-0003-0790-9017</orcidid><orcidid>https://orcid.org/0000-0003-4332-5254</orcidid><orcidid>https://orcid.org/0000-0002-6129-8299</orcidid><orcidid>https://orcid.org/0000-0001-5236-5085</orcidid><orcidid>https://orcid.org/0000-0002-9807-2875</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1347-9032 |
| ispartof | Cancer science, 2022-01, Vol.113 (1), p.334-348 |
| issn | 1347-9032 1349-7006 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8748251 |
| source | MEDLINE; Wiley Online Library Open Access; DOAJ Directory of Open Access Journals; Wiley Online Library Journals Frontfile Complete; PubMed Central |
| subjects | Adaptive Immunity Adolescent Adult Aged Aged, 80 and over Apoptosis B-cell lymphoma C-Reactive Protein - genetics CD16 antigen CD163 antigen Cell death Cell survival Cytokines Dehydrogenases diffuse large B‐cell lymphoma Epstein-Barr virus Epstein-Barr Virus Infections - genetics Epstein-Barr Virus Infections - immunology Female Foxp3 protein Gene expression Gene Expression Regulation, Neoplastic Herpesvirus 4, Human - genetics Humans IL‐10 Immunity, Innate Immunohistochemistry Infiltration Ligands Lymphocytes T Lymphoma Lymphoma, Large B-Cell, Diffuse - genetics Lymphoma, Large B-Cell, Diffuse - immunology Lymphoma, Large B-Cell, Diffuse - virology Macrophages Male Medical prognosis Metastases Microenvironments Middle Aged Multivariate analysis Myc protein Original Pathogenesis PD‐L1, CD163 Pentraxins Prognosis Proteins PTX3 RNA viruses RNA, Viral - genetics Serum Amyloid P-Component - genetics Survival Analysis Tumor Microenvironment Tumor necrosis factor-TNF Tumor-Associated Macrophages - immunology Tumors Up-Regulation Young Adult |
| title | High PTX3 expression is associated with a poor prognosis in diffuse large B‐cell lymphoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-10T10%3A37%3A49IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High%20PTX3%20expression%20is%20associated%20with%20a%20poor%20prognosis%20in%20diffuse%20large%20B%E2%80%90cell%20lymphoma&rft.jtitle=Cancer%20science&rft.au=Carreras,%20Joaquim&rft.date=2022-01&rft.volume=113&rft.issue=1&rft.spage=334&rft.epage=348&rft.pages=334-348&rft.issn=1347-9032&rft.eissn=1349-7006&rft_id=info:doi/10.1111/cas.15179&rft_dat=%3Cproquest_pubme%3E2618379925%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2618379925&rft_id=info:pmid/34706126&rfr_iscdi=true |