High tissue expression of TLRs combined with high density of tumor infiltrating lymphocytes predicts a better prognosis in colorectal cancer patients
Colorectal cancer causes 935,000 cancer deaths yearly. High local immune cell infiltration serves as a positive prognostic factor in CRC. Toll-like receptors (TLRs) induce innate immune responses and lead to adaptive immune system activation. TLRs play protumorigenic and antitumorigenic roles. We ai...
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| Veröffentlicht in: | PloS one 2023-01, Vol.18 (1), p.e0280085-e0280085 |
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| creator | Beilmann-Lehtonen, Ines Kasurinen, Jussi Hagström, Jaana Kaprio, Tuomas Böckelman, Camilla Haglund, Caj |
| description | Colorectal cancer causes 935,000 cancer deaths yearly. High local immune cell infiltration serves as a positive prognostic factor in CRC. Toll-like receptors (TLRs) induce innate immune responses and lead to adaptive immune system activation. TLRs play protumorigenic and antitumorigenic roles. We aimed to explore the relationship between TLR immunoexpressions and the infiltration densities of T-lymphocytes in CRC.
Immunohistochemical TLR2, TLR4, TLR5, and TLR7 positivity and the density of CD3- and CD8-positive cells in tumoral and stromal tissue were evaluated from the tissue microarray slides of 549 consecutive CRC surgical patients treated at Helsinki University Hospital, Finland, between 1998 and 2005. We calculated the associations and correlations using Pearson's chi-square and Spearman's correlation tests, generating survival curves using the Kaplan-Meier method.
Positive intratumoral CD3 and CD8 densities associated with a high TLR2 expression (p < 0.001 and p = 0.001, respectively) and a high TLR4 expression (p = 0.013 and p = 0.025). A low TLR5 immunoexpression associated with negative intratumoral CD3 (p = 0.001) and CD8 (p = 0.011) and a low stromal CD3 (p = 0.001). No association or correlation emerged between TLR7 immunoexpression and CD3 or CD8 cell density. A low CD3-CD8 tumor-stroma index indicated a worse prognosis among all TLR subgroups, except the TLR7-negative subgroup.
We detected significant associations and correlations between high tissue TLR2, TLR4, and TLR5 immunoexpressions and high densities of CD3- and CD8-positive cells. Combining these markers may improve the prognostic evaluation of CRC patients. |
| doi_str_mv | 10.1371/journal.pone.0280085 |
| format | Article |
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Immunohistochemical TLR2, TLR4, TLR5, and TLR7 positivity and the density of CD3- and CD8-positive cells in tumoral and stromal tissue were evaluated from the tissue microarray slides of 549 consecutive CRC surgical patients treated at Helsinki University Hospital, Finland, between 1998 and 2005. We calculated the associations and correlations using Pearson's chi-square and Spearman's correlation tests, generating survival curves using the Kaplan-Meier method.
Positive intratumoral CD3 and CD8 densities associated with a high TLR2 expression (p < 0.001 and p = 0.001, respectively) and a high TLR4 expression (p = 0.013 and p = 0.025). A low TLR5 immunoexpression associated with negative intratumoral CD3 (p = 0.001) and CD8 (p = 0.011) and a low stromal CD3 (p = 0.001). No association or correlation emerged between TLR7 immunoexpression and CD3 or CD8 cell density. A low CD3-CD8 tumor-stroma index indicated a worse prognosis among all TLR subgroups, except the TLR7-negative subgroup.
We detected significant associations and correlations between high tissue TLR2, TLR4, and TLR5 immunoexpressions and high densities of CD3- and CD8-positive cells. Combining these markers may improve the prognostic evaluation of CRC patients.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0280085</identifier><identifier>PMID: 36649244</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adaptive systems ; Antibodies ; Antigens ; Biology and Life Sciences ; Biomarkers, Tumor - metabolism ; Cancer ; CD3 antigen ; CD8 antigen ; CD8-Positive T-Lymphocytes ; Cell density ; Chi-square test ; Cloning ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - pathology ; Correlation ; Dendritic cells ; Density ; Health aspects ; Humans ; Immune response ; Immune system ; Infiltration ; Innate immunity ; Lymphocytes ; Lymphocytes T ; Lymphocytes, Tumor-Infiltrating ; Medical prognosis ; Medicine and Health Sciences ; Metastases ; Pathogens ; Physical Sciences ; Prognosis ; Proteins ; Research and Analysis Methods ; Stroma ; Subgroups ; Tissues ; TLR2 protein ; TLR4 protein ; TLR5 protein ; TLR7 protein ; Toll-Like Receptor 2 - metabolism ; Toll-Like Receptor 4 - metabolism ; Toll-Like Receptor 5 - metabolism ; Toll-Like Receptor 7 - metabolism ; Toll-like receptors ; Toll-Like Receptors - metabolism ; Tumors</subject><ispartof>PloS one, 2023-01, Vol.18 (1), p.e0280085-e0280085</ispartof><rights>Copyright: © 2023 Beilmann-Lehtonen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2023 Public Library of Science</rights><rights>2023 Beilmann-Lehtonen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 Beilmann-Lehtonen et al 2023 Beilmann-Lehtonen et al</rights><rights>2023 Beilmann-Lehtonen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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-c692t-ccc0079fea0f1a916ce3890f143afa805c07207b9b29d3d9a8c013e7353e33ee3</citedby><cites>FETCH-LOGICAL-c692t-ccc0079fea0f1a916ce3890f143afa805c07207b9b29d3d9a8c013e7353e33ee3</cites><orcidid>0000-0001-9183-3128</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/PMC9844887/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9844887/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,2103,2929,23870,27928,27929,53795,53797</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36649244$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Patel, Girijesh Kumar</contributor><creatorcontrib>Beilmann-Lehtonen, Ines</creatorcontrib><creatorcontrib>Kasurinen, Jussi</creatorcontrib><creatorcontrib>Hagström, Jaana</creatorcontrib><creatorcontrib>Kaprio, Tuomas</creatorcontrib><creatorcontrib>Böckelman, Camilla</creatorcontrib><creatorcontrib>Haglund, Caj</creatorcontrib><title>High tissue expression of TLRs combined with high density of tumor infiltrating lymphocytes predicts a better prognosis in colorectal cancer patients</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Colorectal cancer causes 935,000 cancer deaths yearly. High local immune cell infiltration serves as a positive prognostic factor in CRC. Toll-like receptors (TLRs) induce innate immune responses and lead to adaptive immune system activation. TLRs play protumorigenic and antitumorigenic roles. We aimed to explore the relationship between TLR immunoexpressions and the infiltration densities of T-lymphocytes in CRC.
Immunohistochemical TLR2, TLR4, TLR5, and TLR7 positivity and the density of CD3- and CD8-positive cells in tumoral and stromal tissue were evaluated from the tissue microarray slides of 549 consecutive CRC surgical patients treated at Helsinki University Hospital, Finland, between 1998 and 2005. We calculated the associations and correlations using Pearson's chi-square and Spearman's correlation tests, generating survival curves using the Kaplan-Meier method.
Positive intratumoral CD3 and CD8 densities associated with a high TLR2 expression (p < 0.001 and p = 0.001, respectively) and a high TLR4 expression (p = 0.013 and p = 0.025). A low TLR5 immunoexpression associated with negative intratumoral CD3 (p = 0.001) and CD8 (p = 0.011) and a low stromal CD3 (p = 0.001). No association or correlation emerged between TLR7 immunoexpression and CD3 or CD8 cell density. A low CD3-CD8 tumor-stroma index indicated a worse prognosis among all TLR subgroups, except the TLR7-negative subgroup.
We detected significant associations and correlations between high tissue TLR2, TLR4, and TLR5 immunoexpressions and high densities of CD3- and CD8-positive cells. Combining these markers may improve the prognostic evaluation of CRC patients.</description><subject>Adaptive systems</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Biology and Life Sciences</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Cancer</subject><subject>CD3 antigen</subject><subject>CD8 antigen</subject><subject>CD8-Positive T-Lymphocytes</subject><subject>Cell density</subject><subject>Chi-square test</subject><subject>Cloning</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - pathology</subject><subject>Correlation</subject><subject>Dendritic cells</subject><subject>Density</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immune system</subject><subject>Infiltration</subject><subject>Innate immunity</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Lymphocytes, Tumor-Infiltrating</subject><subject>Medical prognosis</subject><subject>Medicine and Health Sciences</subject><subject>Metastases</subject><subject>Pathogens</subject><subject>Physical Sciences</subject><subject>Prognosis</subject><subject>Proteins</subject><subject>Research and Analysis Methods</subject><subject>Stroma</subject><subject>Subgroups</subject><subject>Tissues</subject><subject>TLR2 protein</subject><subject>TLR4 protein</subject><subject>TLR5 protein</subject><subject>TLR7 protein</subject><subject>Toll-Like Receptor 2 - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Beilmann-Lehtonen, Ines</au><au>Kasurinen, Jussi</au><au>Hagström, Jaana</au><au>Kaprio, Tuomas</au><au>Böckelman, Camilla</au><au>Haglund, Caj</au><au>Patel, Girijesh Kumar</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High tissue expression of TLRs combined with high density of tumor infiltrating lymphocytes predicts a better prognosis in colorectal cancer patients</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2023-01-17</date><risdate>2023</risdate><volume>18</volume><issue>1</issue><spage>e0280085</spage><epage>e0280085</epage><pages>e0280085-e0280085</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Colorectal cancer causes 935,000 cancer deaths yearly. High local immune cell infiltration serves as a positive prognostic factor in CRC. Toll-like receptors (TLRs) induce innate immune responses and lead to adaptive immune system activation. TLRs play protumorigenic and antitumorigenic roles. We aimed to explore the relationship between TLR immunoexpressions and the infiltration densities of T-lymphocytes in CRC.
Immunohistochemical TLR2, TLR4, TLR5, and TLR7 positivity and the density of CD3- and CD8-positive cells in tumoral and stromal tissue were evaluated from the tissue microarray slides of 549 consecutive CRC surgical patients treated at Helsinki University Hospital, Finland, between 1998 and 2005. We calculated the associations and correlations using Pearson's chi-square and Spearman's correlation tests, generating survival curves using the Kaplan-Meier method.
Positive intratumoral CD3 and CD8 densities associated with a high TLR2 expression (p < 0.001 and p = 0.001, respectively) and a high TLR4 expression (p = 0.013 and p = 0.025). A low TLR5 immunoexpression associated with negative intratumoral CD3 (p = 0.001) and CD8 (p = 0.011) and a low stromal CD3 (p = 0.001). No association or correlation emerged between TLR7 immunoexpression and CD3 or CD8 cell density. A low CD3-CD8 tumor-stroma index indicated a worse prognosis among all TLR subgroups, except the TLR7-negative subgroup.
We detected significant associations and correlations between high tissue TLR2, TLR4, and TLR5 immunoexpressions and high densities of CD3- and CD8-positive cells. Combining these markers may improve the prognostic evaluation of CRC patients.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>36649244</pmid><doi>10.1371/journal.pone.0280085</doi><orcidid>https://orcid.org/0000-0001-9183-3128</orcidid><oa>free_for_read</oa></addata></record> |
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| language | eng |
| recordid | cdi_plos_journals_2766403745 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adaptive systems Antibodies Antigens Biology and Life Sciences Biomarkers, Tumor - metabolism Cancer CD3 antigen CD8 antigen CD8-Positive T-Lymphocytes Cell density Chi-square test Cloning Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - pathology Correlation Dendritic cells Density Health aspects Humans Immune response Immune system Infiltration Innate immunity Lymphocytes Lymphocytes T Lymphocytes, Tumor-Infiltrating Medical prognosis Medicine and Health Sciences Metastases Pathogens Physical Sciences Prognosis Proteins Research and Analysis Methods Stroma Subgroups Tissues TLR2 protein TLR4 protein TLR5 protein TLR7 protein Toll-Like Receptor 2 - metabolism Toll-Like Receptor 4 - metabolism Toll-Like Receptor 5 - metabolism Toll-Like Receptor 7 - metabolism Toll-like receptors Toll-Like Receptors - metabolism Tumors |
| title | High tissue expression of TLRs combined with high density of tumor infiltrating lymphocytes predicts a better prognosis in colorectal cancer patients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-17T09%3A54%3A28IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=High%20tissue%20expression%20of%20TLRs%20combined%20with%20high%20density%20of%20tumor%20infiltrating%20lymphocytes%20predicts%20a%20better%20prognosis%20in%20colorectal%20cancer%20patients&rft.jtitle=PloS%20one&rft.au=Beilmann-Lehtonen,%20Ines&rft.date=2023-01-17&rft.volume=18&rft.issue=1&rft.spage=e0280085&rft.epage=e0280085&rft.pages=e0280085-e0280085&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0280085&rft_dat=%3Cgale_plos_%3EA733560411%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2766403745&rft_id=info:pmid/36649244&rft_galeid=A733560411&rft_doaj_id=oai_doaj_org_article_5056c2f792124aa6b072ca00b89dfbfc&rfr_iscdi=true |