Increased CD3+, CD8+, or FoxP3+ T lymphocyte infiltrations are associated with the pathogenesis of colorectal cancer but not with the overall survival of patients
Tumor-infiltrating lymphocytes include heterogeneous populations of T lymphocytes that play crucial roles in the tumor immune response; importantly, their presence in the tumor tissue may predict clinical outcomes. Therefore, we herein studied the prognostic significance of the presence and location...
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creator | Barbosa, Ana Margarida Martins Martinho, Olga Cardoso, Rosete Maria Amorim Novais Nogueira Campos, Juliana Lobo, Liliana Pinto, Henrique Longatto, Adhemar Castro, António G. Martins, Sandra Torrado, Egídio |
description | Tumor-infiltrating lymphocytes include heterogeneous populations of T lymphocytes that play crucial roles in the tumor immune response; importantly, their presence in the tumor tissue may predict clinical outcomes. Therefore, we herein studied the prognostic significance of the presence and location of CD3 + , CD8 + , and FoxP3 + T lymphocytes in colorectal cancer samples. In the intratumor analysis, our data did not reveal any association between lymphocyte infiltrations with clinical or pathological data. However, in the tumor margins, we found that the presence of high infiltrations of CD3 + , CD8 + , or FoxP3 + T lymphocytes were associated with TNM stages I-II ( p = 0.021, p = 0.022, and p = 0.012, respectively) and absence of lymph node metastases ( p = 0.010, p = 0.003, and p = 0.004, respectively). Despite these associations with good prognostic indicators, we were not able to find any statistically significant alterations in the overall survival of the patients, even though high infiltrations of FoxP3 + T lymphocytes in the tumor margins resulted in an increased overall survival of 14 months. Taken together, these data show that the presence of CD3 + , CD8 + , or FoxP3 + T lymphocyte infiltrates in the tumor margins are associated with the pathogenesis of CRC, but only high Foxp3 + T lymphocyte infiltrations in the tumor invasive margins are inclined to indicate favorable prognosis.
This work was supported by National funds through the Foundation for Science and Technology (FCT)—projects PTDC/MED-ONC/28658/2017, UIDB/50026/2020, and UIDP/50026/2020; and by the Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) projects NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023. AMB was supported by the FCT fellowship SFRH/BD/120371/2016 and ET by the FCT investigator grant IF/01390/2014 and Estímulo Individual ao Emprego Científico CEECIND/03070/2020. |
doi_str_mv | 10.3390/biology10080808 |
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This work was supported by National funds through the Foundation for Science and Technology (FCT)—projects PTDC/MED-ONC/28658/2017, UIDB/50026/2020, and UIDP/50026/2020; and by the Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) projects NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023. AMB was supported by the FCT fellowship SFRH/BD/120371/2016 and ET by the FCT investigator grant IF/01390/2014 and Estímulo Individual ao Emprego Científico CEECIND/03070/2020.</description><identifier>ISSN: 2079-7737</identifier><identifier>EISSN: 2079-7737</identifier><identifier>DOI: 10.3390/biology10080808</identifier><identifier>PMID: 34440038</identifier><language>eng</language><publisher>Basel: Multidisciplinary Digital Publishing Institute (MDPI)</publisher><subject>Antibodies ; Cancer ; CD3 antigen ; CD8 antigen ; Clinicopathological features ; Colorectal cancer ; Colorectal carcinoma ; Committees ; Ethics ; Foxp3 protein ; Immune response ; Infiltration ; Invasiveness ; Lymph nodes ; Lymphocytes ; Lymphocytes T ; Medical prognosis ; Metastases ; Pathogenesis ; Patients ; Prognosis ; Prognostic indicators ; Science & Technology ; Statistical analysis ; Survival analysis ; T lymphocytes ; Tumor-infiltrating lymphocytes ; Tumors</subject><ispartof>Biology (Basel, Switzerland), 2021-08, Vol.10 (8), p.1-16</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c489t-a483cf7603803a4e2a5a62e4635cfea40206355ac71543995c7917b355d16ae3</citedby><cites>FETCH-LOGICAL-c489t-a483cf7603803a4e2a5a62e4635cfea40206355ac71543995c7917b355d16ae3</cites><orcidid>0000-0002-5779-9752 ; 0000-0002-3221-0403 ; 0000-0002-3526-3199</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/PMC8389643/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8389643/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,724,777,781,861,882,2096,27905,27906,53772,53774</link.rule.ids></links><search><creatorcontrib>Barbosa, Ana Margarida Martins</creatorcontrib><creatorcontrib>Martinho, Olga</creatorcontrib><creatorcontrib>Cardoso, Rosete Maria Amorim Novais Nogueira</creatorcontrib><creatorcontrib>Campos, Juliana</creatorcontrib><creatorcontrib>Lobo, Liliana</creatorcontrib><creatorcontrib>Pinto, Henrique</creatorcontrib><creatorcontrib>Longatto, Adhemar</creatorcontrib><creatorcontrib>Castro, António G.</creatorcontrib><creatorcontrib>Martins, Sandra</creatorcontrib><creatorcontrib>Torrado, Egídio</creatorcontrib><title>Increased CD3+, CD8+, or FoxP3+ T lymphocyte infiltrations are associated with the pathogenesis of colorectal cancer but not with the overall survival of patients</title><title>Biology (Basel, Switzerland)</title><description>Tumor-infiltrating lymphocytes include heterogeneous populations of T lymphocytes that play crucial roles in the tumor immune response; importantly, their presence in the tumor tissue may predict clinical outcomes. Therefore, we herein studied the prognostic significance of the presence and location of CD3 + , CD8 + , and FoxP3 + T lymphocytes in colorectal cancer samples. In the intratumor analysis, our data did not reveal any association between lymphocyte infiltrations with clinical or pathological data. However, in the tumor margins, we found that the presence of high infiltrations of CD3 + , CD8 + , or FoxP3 + T lymphocytes were associated with TNM stages I-II ( p = 0.021, p = 0.022, and p = 0.012, respectively) and absence of lymph node metastases ( p = 0.010, p = 0.003, and p = 0.004, respectively). Despite these associations with good prognostic indicators, we were not able to find any statistically significant alterations in the overall survival of the patients, even though high infiltrations of FoxP3 + T lymphocytes in the tumor margins resulted in an increased overall survival of 14 months. Taken together, these data show that the presence of CD3 + , CD8 + , or FoxP3 + T lymphocyte infiltrates in the tumor margins are associated with the pathogenesis of CRC, but only high Foxp3 + T lymphocyte infiltrations in the tumor invasive margins are inclined to indicate favorable prognosis.
This work was supported by National funds through the Foundation for Science and Technology (FCT)—projects PTDC/MED-ONC/28658/2017, UIDB/50026/2020, and UIDP/50026/2020; and by the Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) projects NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023. 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Martinho, Olga ; Cardoso, Rosete Maria Amorim Novais Nogueira ; Campos, Juliana ; Lobo, Liliana ; Pinto, Henrique ; Longatto, Adhemar ; Castro, António G. ; Martins, Sandra ; Torrado, Egídio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c489t-a483cf7603803a4e2a5a62e4635cfea40206355ac71543995c7917b355d16ae3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Antibodies</topic><topic>Cancer</topic><topic>CD3 antigen</topic><topic>CD8 antigen</topic><topic>Clinicopathological features</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Committees</topic><topic>Ethics</topic><topic>Foxp3 protein</topic><topic>Immune response</topic><topic>Infiltration</topic><topic>Invasiveness</topic><topic>Lymph nodes</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Medical prognosis</topic><topic>Metastases</topic><topic>Pathogenesis</topic><topic>Patients</topic><topic>Prognosis</topic><topic>Prognostic indicators</topic><topic>Science & Technology</topic><topic>Statistical analysis</topic><topic>Survival analysis</topic><topic>T lymphocytes</topic><topic>Tumor-infiltrating lymphocytes</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Barbosa, Ana Margarida Martins</creatorcontrib><creatorcontrib>Martinho, Olga</creatorcontrib><creatorcontrib>Cardoso, Rosete Maria Amorim Novais Nogueira</creatorcontrib><creatorcontrib>Campos, Juliana</creatorcontrib><creatorcontrib>Lobo, Liliana</creatorcontrib><creatorcontrib>Pinto, Henrique</creatorcontrib><creatorcontrib>Longatto, Adhemar</creatorcontrib><creatorcontrib>Castro, António G.</creatorcontrib><creatorcontrib>Martins, Sandra</creatorcontrib><creatorcontrib>Torrado, Egídio</creatorcontrib><collection>RCAAP open access repository</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Technology Research Database</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>Engineering Research Database</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Biology (Basel, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Barbosa, Ana Margarida Martins</au><au>Martinho, Olga</au><au>Cardoso, Rosete Maria Amorim Novais Nogueira</au><au>Campos, Juliana</au><au>Lobo, Liliana</au><au>Pinto, Henrique</au><au>Longatto, Adhemar</au><au>Castro, António G.</au><au>Martins, Sandra</au><au>Torrado, Egídio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Increased CD3+, CD8+, or FoxP3+ T lymphocyte infiltrations are associated with the pathogenesis of colorectal cancer but not with the overall survival of patients</atitle><jtitle>Biology (Basel, Switzerland)</jtitle><date>2021-08-20</date><risdate>2021</risdate><volume>10</volume><issue>8</issue><spage>1</spage><epage>16</epage><pages>1-16</pages><issn>2079-7737</issn><eissn>2079-7737</eissn><abstract>Tumor-infiltrating lymphocytes include heterogeneous populations of T lymphocytes that play crucial roles in the tumor immune response; importantly, their presence in the tumor tissue may predict clinical outcomes. Therefore, we herein studied the prognostic significance of the presence and location of CD3 + , CD8 + , and FoxP3 + T lymphocytes in colorectal cancer samples. In the intratumor analysis, our data did not reveal any association between lymphocyte infiltrations with clinical or pathological data. However, in the tumor margins, we found that the presence of high infiltrations of CD3 + , CD8 + , or FoxP3 + T lymphocytes were associated with TNM stages I-II ( p = 0.021, p = 0.022, and p = 0.012, respectively) and absence of lymph node metastases ( p = 0.010, p = 0.003, and p = 0.004, respectively). Despite these associations with good prognostic indicators, we were not able to find any statistically significant alterations in the overall survival of the patients, even though high infiltrations of FoxP3 + T lymphocytes in the tumor margins resulted in an increased overall survival of 14 months. Taken together, these data show that the presence of CD3 + , CD8 + , or FoxP3 + T lymphocyte infiltrates in the tumor margins are associated with the pathogenesis of CRC, but only high Foxp3 + T lymphocyte infiltrations in the tumor invasive margins are inclined to indicate favorable prognosis.
This work was supported by National funds through the Foundation for Science and Technology (FCT)—projects PTDC/MED-ONC/28658/2017, UIDB/50026/2020, and UIDP/50026/2020; and by the Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) projects NORTE-01-0145-FEDER-000013 and NORTE-01-0145-FEDER-000023. AMB was supported by the FCT fellowship SFRH/BD/120371/2016 and ET by the FCT investigator grant IF/01390/2014 and Estímulo Individual ao Emprego Científico CEECIND/03070/2020.</abstract><cop>Basel</cop><pub>Multidisciplinary Digital Publishing Institute (MDPI)</pub><pmid>34440038</pmid><doi>10.3390/biology10080808</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0002-5779-9752</orcidid><orcidid>https://orcid.org/0000-0002-3221-0403</orcidid><orcidid>https://orcid.org/0000-0002-3526-3199</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Antibodies Cancer CD3 antigen CD8 antigen Clinicopathological features Colorectal cancer Colorectal carcinoma Committees Ethics Foxp3 protein Immune response Infiltration Invasiveness Lymph nodes Lymphocytes Lymphocytes T Medical prognosis Metastases Pathogenesis Patients Prognosis Prognostic indicators Science & Technology Statistical analysis Survival analysis T lymphocytes Tumor-infiltrating lymphocytes Tumors |
title | Increased CD3+, CD8+, or FoxP3+ T lymphocyte infiltrations are associated with the pathogenesis of colorectal cancer but not with the overall survival of patients |
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