Prognostic impacts of tumoral expression and serum levels of PD-L1 and CTLA-4 in colorectal cancer patients
Background Programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) play a pivotal role in cancer immunotherapy. Each of these molecules has a membrane-bound receptor form (mPD-L1/mCTLA-4) and a soluble form (sPD-L1/sCTLA-4). However, these prognostic impacts i...
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| Veröffentlicht in: | Cancer Immunology, Immunotherapy Immunotherapy, 2020-12, Vol.69 (12), p.2533-2546 |
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| creator | Omura, Yusuke Toiyama, Yuji Okugawa, Yoshinaga Yin, Chengzeng Shigemori, Tsunehiko Kusunoki, Kurando Kusunoki, Yukina Ide, Shozo Shimura, Tadanobu Fujikawa, Hiroyuki Yasuda, Hiromi Hiro, Junichiro Ohi, Masaki Kusunoki, Masato |
| description | Background
Programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) play a pivotal role in cancer immunotherapy. Each of these molecules has a membrane-bound receptor form (mPD-L1/mCTLA-4) and a soluble form (sPD-L1/sCTLA-4). However, these prognostic impacts in colorectal cancer (CRC) remain unclear.
Methods
We immunohistochemically scored tumoral mPD-L1/mCTLA-4 expression and quantified preoperative circulating sPD-L1/sCTLA-4 levels using matched serum specimens from 131 patients with pStage I–III CRC. We also examined the association between these statuses and tumor infiltrating lymphocytes (TILs) in these patients.
Results
Elevated levels of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 were significantly correlated with poor overall survival (OS) and disease-free survival (DFS). Co-high expression of tumoral mPD-L1 and mCTLA-4 or co-elevated levels of serum sPD-L1 and sCTLA-4 were strongly correlated with poor OS and DFS. Multivariate analysis revealed that both statuses were negative independent prognostic factors for OS [hazard ratio (HR) 3.86, 95% confidence interval (95% CI) 1.71–8.51,
p
= 0.001; HR 5.72, 95% CI 1.87–14.54,
p
= 0.004, respectively] and DFS (HR 2.53, 95% CI 1.23–4.95,
p
= 0.01; HR 6.88, 95% CI 2.42–17.13,
p
= 0.0008, respectively). Although low expression of tumoral mCTLA-4 was significantly correlated with increased CD8(+) TILs, there was no correlation in any other combination.
Conclusions
We verified the prognostic impacts of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 in pStage I–III CRC patients. Dual evaluation of immune checkpoint molecules in primary tissues or preoperative serum could identify a patient population with poor prognosis in these patients. |
| doi_str_mv | 10.1007/s00262-020-02645-1 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11027465</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2473374864</sourcerecordid><originalsourceid>FETCH-LOGICAL-c581t-3e3ff9da70e1b84999632a8cac2c9212f54a819499691b0426cf68a6e41400563</originalsourceid><addsrcrecordid>eNp9kc1u1DAUhS0EokPhBVggS2zYBO61HSdeoWpKAWkkuihry-O5GVISO9hJVd4eM1PKz4KFZcvnu8c-Oow9R3iNAM2bDCC0qEBAWVrVFT5gK1SyXLU1PmQrkAqqBkCdsCc5X5eDAGMesxMp6qZpUa_Y18sU9yHmufe8Hyfn58xjx-dljMkNnG6nRDn3MXAXdjxTWkY-0A0NB-zyvNrgQVlfbc4qxfvAfRxiIj-Xae-Cp8QnN_cU5vyUPerckOnZ3X7KPl-8u1p_qDaf3n9cn20qX7c4V5Jk15mda4Bw2ypjjJbCtd554Y1A0dXKtWiKoA1uSybtO906TQoVQK3lKXt79J2W7Ug7X94uWeyU-tGl7za63v6thP6L3ccbiwiiUbouDq_uHFL8tlCe7dhnT8PgAsUlW6FQGwmmFgV9-Q96HZcUSr5CNVI2qtWqUOJI-RRzTtTd_wbB_izTHsu0pUx7KNNiGXrxZ477kV_tFUAegVyksKf0--3_2P4AHC6pZQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2473374864</pqid></control><display><type>article</type><title>Prognostic impacts of tumoral expression and serum levels of PD-L1 and CTLA-4 in colorectal cancer patients</title><source>MEDLINE</source><source>SpringerLink (Online service)</source><source>PubMed Central</source><creator>Omura, Yusuke ; Toiyama, Yuji ; Okugawa, Yoshinaga ; Yin, Chengzeng ; Shigemori, Tsunehiko ; Kusunoki, Kurando ; Kusunoki, Yukina ; Ide, Shozo ; Shimura, Tadanobu ; Fujikawa, Hiroyuki ; Yasuda, Hiromi ; Hiro, Junichiro ; Ohi, Masaki ; Kusunoki, Masato</creator><creatorcontrib>Omura, Yusuke ; Toiyama, Yuji ; Okugawa, Yoshinaga ; Yin, Chengzeng ; Shigemori, Tsunehiko ; Kusunoki, Kurando ; Kusunoki, Yukina ; Ide, Shozo ; Shimura, Tadanobu ; Fujikawa, Hiroyuki ; Yasuda, Hiromi ; Hiro, Junichiro ; Ohi, Masaki ; Kusunoki, Masato</creatorcontrib><description>Background
Programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) play a pivotal role in cancer immunotherapy. Each of these molecules has a membrane-bound receptor form (mPD-L1/mCTLA-4) and a soluble form (sPD-L1/sCTLA-4). However, these prognostic impacts in colorectal cancer (CRC) remain unclear.
Methods
We immunohistochemically scored tumoral mPD-L1/mCTLA-4 expression and quantified preoperative circulating sPD-L1/sCTLA-4 levels using matched serum specimens from 131 patients with pStage I–III CRC. We also examined the association between these statuses and tumor infiltrating lymphocytes (TILs) in these patients.
Results
Elevated levels of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 were significantly correlated with poor overall survival (OS) and disease-free survival (DFS). Co-high expression of tumoral mPD-L1 and mCTLA-4 or co-elevated levels of serum sPD-L1 and sCTLA-4 were strongly correlated with poor OS and DFS. Multivariate analysis revealed that both statuses were negative independent prognostic factors for OS [hazard ratio (HR) 3.86, 95% confidence interval (95% CI) 1.71–8.51,
p
= 0.001; HR 5.72, 95% CI 1.87–14.54,
p
= 0.004, respectively] and DFS (HR 2.53, 95% CI 1.23–4.95,
p
= 0.01; HR 6.88, 95% CI 2.42–17.13,
p
= 0.0008, respectively). Although low expression of tumoral mCTLA-4 was significantly correlated with increased CD8(+) TILs, there was no correlation in any other combination.
Conclusions
We verified the prognostic impacts of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 in pStage I–III CRC patients. Dual evaluation of immune checkpoint molecules in primary tissues or preoperative serum could identify a patient population with poor prognosis in these patients.</description><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-020-02645-1</identifier><identifier>PMID: 32577816</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Apoptosis ; B7-H1 Antigen - blood ; B7-H1 Antigen - immunology ; B7-H1 Antigen - metabolism ; Biomarkers, Tumor - blood ; Biomarkers, Tumor - immunology ; Biomarkers, Tumor - metabolism ; Cancer ; Cancer immunotherapy ; Cancer Research ; CD8 antigen ; Cell death ; Colon - immunology ; Colon - pathology ; Colon - surgery ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - blood ; Colorectal Neoplasms - immunology ; Colorectal Neoplasms - mortality ; Colorectal Neoplasms - surgery ; CTLA-4 Antigen - blood ; CTLA-4 Antigen - immunology ; CTLA-4 Antigen - metabolism ; CTLA-4 protein ; Cytotoxicity ; Disease-Free Survival ; Female ; Humans ; Immune checkpoint ; Immunology ; Immunotherapy ; Kaplan-Meier Estimate ; Lymphocytes T ; Lymphocytes, Tumor-Infiltrating - immunology ; Lymphocytes, Tumor-Infiltrating - metabolism ; Male ; Medical prognosis ; Medicine ; Medicine & Public Health ; Middle Aged ; Multivariate analysis ; Neoplasm Staging ; Oncology ; Original ; Original Article ; PD-L1 protein ; Prognosis ; Rectum - immunology ; Rectum - pathology ; Rectum - surgery ; Retrospective Studies ; Serum levels</subject><ispartof>Cancer Immunology, Immunotherapy, 2020-12, Vol.69 (12), p.2533-2546</ispartof><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020</rights><rights>Springer-Verlag GmbH Germany, part of Springer Nature 2020.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c581t-3e3ff9da70e1b84999632a8cac2c9212f54a819499691b0426cf68a6e41400563</citedby><cites>FETCH-LOGICAL-c581t-3e3ff9da70e1b84999632a8cac2c9212f54a819499691b0426cf68a6e41400563</cites><orcidid>0000-0003-1301-3268</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/PMC11027465/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11027465/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,41467,42536,51298,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32577816$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Omura, Yusuke</creatorcontrib><creatorcontrib>Toiyama, Yuji</creatorcontrib><creatorcontrib>Okugawa, Yoshinaga</creatorcontrib><creatorcontrib>Yin, Chengzeng</creatorcontrib><creatorcontrib>Shigemori, Tsunehiko</creatorcontrib><creatorcontrib>Kusunoki, Kurando</creatorcontrib><creatorcontrib>Kusunoki, Yukina</creatorcontrib><creatorcontrib>Ide, Shozo</creatorcontrib><creatorcontrib>Shimura, Tadanobu</creatorcontrib><creatorcontrib>Fujikawa, Hiroyuki</creatorcontrib><creatorcontrib>Yasuda, Hiromi</creatorcontrib><creatorcontrib>Hiro, Junichiro</creatorcontrib><creatorcontrib>Ohi, Masaki</creatorcontrib><creatorcontrib>Kusunoki, Masato</creatorcontrib><title>Prognostic impacts of tumoral expression and serum levels of PD-L1 and CTLA-4 in colorectal cancer patients</title><title>Cancer Immunology, Immunotherapy</title><addtitle>Cancer Immunol Immunother</addtitle><addtitle>Cancer Immunol Immunother</addtitle><description>Background
Programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) play a pivotal role in cancer immunotherapy. Each of these molecules has a membrane-bound receptor form (mPD-L1/mCTLA-4) and a soluble form (sPD-L1/sCTLA-4). However, these prognostic impacts in colorectal cancer (CRC) remain unclear.
Methods
We immunohistochemically scored tumoral mPD-L1/mCTLA-4 expression and quantified preoperative circulating sPD-L1/sCTLA-4 levels using matched serum specimens from 131 patients with pStage I–III CRC. We also examined the association between these statuses and tumor infiltrating lymphocytes (TILs) in these patients.
Results
Elevated levels of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 were significantly correlated with poor overall survival (OS) and disease-free survival (DFS). Co-high expression of tumoral mPD-L1 and mCTLA-4 or co-elevated levels of serum sPD-L1 and sCTLA-4 were strongly correlated with poor OS and DFS. Multivariate analysis revealed that both statuses were negative independent prognostic factors for OS [hazard ratio (HR) 3.86, 95% confidence interval (95% CI) 1.71–8.51,
p
= 0.001; HR 5.72, 95% CI 1.87–14.54,
p
= 0.004, respectively] and DFS (HR 2.53, 95% CI 1.23–4.95,
p
= 0.01; HR 6.88, 95% CI 2.42–17.13,
p
= 0.0008, respectively). Although low expression of tumoral mCTLA-4 was significantly correlated with increased CD8(+) TILs, there was no correlation in any other combination.
Conclusions
We verified the prognostic impacts of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 in pStage I–III CRC patients. Dual evaluation of immune checkpoint molecules in primary tissues or preoperative serum could identify a patient population with poor prognosis in these patients.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Apoptosis</subject><subject>B7-H1 Antigen - blood</subject><subject>B7-H1 Antigen - immunology</subject><subject>B7-H1 Antigen - metabolism</subject><subject>Biomarkers, Tumor - blood</subject><subject>Biomarkers, Tumor - immunology</subject><subject>Biomarkers, Tumor - metabolism</subject><subject>Cancer</subject><subject>Cancer immunotherapy</subject><subject>Cancer Research</subject><subject>CD8 antigen</subject><subject>Cell death</subject><subject>Colon - immunology</subject><subject>Colon - pathology</subject><subject>Colon - surgery</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - blood</subject><subject>Colorectal Neoplasms - immunology</subject><subject>Colorectal Neoplasms - mortality</subject><subject>Colorectal Neoplasms - surgery</subject><subject>CTLA-4 Antigen - blood</subject><subject>CTLA-4 Antigen - immunology</subject><subject>CTLA-4 Antigen - metabolism</subject><subject>CTLA-4 protein</subject><subject>Cytotoxicity</subject><subject>Disease-Free Survival</subject><subject>Female</subject><subject>Humans</subject><subject>Immune checkpoint</subject><subject>Immunology</subject><subject>Immunotherapy</subject><subject>Kaplan-Meier Estimate</subject><subject>Lymphocytes T</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Lymphocytes, Tumor-Infiltrating - metabolism</subject><subject>Male</subject><subject>Medical prognosis</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Middle Aged</subject><subject>Multivariate analysis</subject><subject>Neoplasm Staging</subject><subject>Oncology</subject><subject>Original</subject><subject>Original Article</subject><subject>PD-L1 protein</subject><subject>Prognosis</subject><subject>Rectum - immunology</subject><subject>Rectum - pathology</subject><subject>Rectum - surgery</subject><subject>Retrospective Studies</subject><subject>Serum levels</subject><issn>0340-7004</issn><issn>1432-0851</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kc1u1DAUhS0EokPhBVggS2zYBO61HSdeoWpKAWkkuihry-O5GVISO9hJVd4eM1PKz4KFZcvnu8c-Oow9R3iNAM2bDCC0qEBAWVrVFT5gK1SyXLU1PmQrkAqqBkCdsCc5X5eDAGMesxMp6qZpUa_Y18sU9yHmufe8Hyfn58xjx-dljMkNnG6nRDn3MXAXdjxTWkY-0A0NB-zyvNrgQVlfbc4qxfvAfRxiIj-Xae-Cp8QnN_cU5vyUPerckOnZ3X7KPl-8u1p_qDaf3n9cn20qX7c4V5Jk15mda4Bw2ypjjJbCtd554Y1A0dXKtWiKoA1uSybtO906TQoVQK3lKXt79J2W7Ug7X94uWeyU-tGl7za63v6thP6L3ccbiwiiUbouDq_uHFL8tlCe7dhnT8PgAsUlW6FQGwmmFgV9-Q96HZcUSr5CNVI2qtWqUOJI-RRzTtTd_wbB_izTHsu0pUx7KNNiGXrxZ477kV_tFUAegVyksKf0--3_2P4AHC6pZQ</recordid><startdate>20201201</startdate><enddate>20201201</enddate><creator>Omura, Yusuke</creator><creator>Toiyama, Yuji</creator><creator>Okugawa, Yoshinaga</creator><creator>Yin, Chengzeng</creator><creator>Shigemori, Tsunehiko</creator><creator>Kusunoki, Kurando</creator><creator>Kusunoki, Yukina</creator><creator>Ide, Shozo</creator><creator>Shimura, Tadanobu</creator><creator>Fujikawa, Hiroyuki</creator><creator>Yasuda, Hiromi</creator><creator>Hiro, Junichiro</creator><creator>Ohi, Masaki</creator><creator>Kusunoki, Masato</creator><general>Springer Berlin Heidelberg</general><general>Springer Nature B.V</general><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>3V.</scope><scope>7T5</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</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>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-1301-3268</orcidid></search><sort><creationdate>20201201</creationdate><title>Prognostic impacts of tumoral expression and serum levels of PD-L1 and CTLA-4 in colorectal cancer patients</title><author>Omura, Yusuke ; Toiyama, Yuji ; Okugawa, Yoshinaga ; Yin, Chengzeng ; Shigemori, Tsunehiko ; Kusunoki, Kurando ; Kusunoki, Yukina ; Ide, Shozo ; Shimura, Tadanobu ; Fujikawa, Hiroyuki ; Yasuda, Hiromi ; Hiro, Junichiro ; Ohi, Masaki ; Kusunoki, Masato</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c581t-3e3ff9da70e1b84999632a8cac2c9212f54a819499691b0426cf68a6e41400563</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Apoptosis</topic><topic>B7-H1 Antigen - blood</topic><topic>B7-H1 Antigen - immunology</topic><topic>B7-H1 Antigen - metabolism</topic><topic>Biomarkers, Tumor - blood</topic><topic>Biomarkers, Tumor - immunology</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Cancer</topic><topic>Cancer immunotherapy</topic><topic>Cancer Research</topic><topic>CD8 antigen</topic><topic>Cell death</topic><topic>Colon - immunology</topic><topic>Colon - pathology</topic><topic>Colon - surgery</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - blood</topic><topic>Colorectal Neoplasms - immunology</topic><topic>Colorectal Neoplasms - mortality</topic><topic>Colorectal Neoplasms - surgery</topic><topic>CTLA-4 Antigen - blood</topic><topic>CTLA-4 Antigen - immunology</topic><topic>CTLA-4 Antigen - metabolism</topic><topic>CTLA-4 protein</topic><topic>Cytotoxicity</topic><topic>Disease-Free Survival</topic><topic>Female</topic><topic>Humans</topic><topic>Immune checkpoint</topic><topic>Immunology</topic><topic>Immunotherapy</topic><topic>Kaplan-Meier Estimate</topic><topic>Lymphocytes T</topic><topic>Lymphocytes, Tumor-Infiltrating - immunology</topic><topic>Lymphocytes, Tumor-Infiltrating - metabolism</topic><topic>Male</topic><topic>Medical prognosis</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Middle Aged</topic><topic>Multivariate analysis</topic><topic>Neoplasm Staging</topic><topic>Oncology</topic><topic>Original</topic><topic>Original Article</topic><topic>PD-L1 protein</topic><topic>Prognosis</topic><topic>Rectum - immunology</topic><topic>Rectum - pathology</topic><topic>Rectum - surgery</topic><topic>Retrospective Studies</topic><topic>Serum levels</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Omura, Yusuke</creatorcontrib><creatorcontrib>Toiyama, Yuji</creatorcontrib><creatorcontrib>Okugawa, Yoshinaga</creatorcontrib><creatorcontrib>Yin, Chengzeng</creatorcontrib><creatorcontrib>Shigemori, Tsunehiko</creatorcontrib><creatorcontrib>Kusunoki, Kurando</creatorcontrib><creatorcontrib>Kusunoki, Yukina</creatorcontrib><creatorcontrib>Ide, Shozo</creatorcontrib><creatorcontrib>Shimura, Tadanobu</creatorcontrib><creatorcontrib>Fujikawa, Hiroyuki</creatorcontrib><creatorcontrib>Yasuda, Hiromi</creatorcontrib><creatorcontrib>Hiro, Junichiro</creatorcontrib><creatorcontrib>Ohi, Masaki</creatorcontrib><creatorcontrib>Kusunoki, Masato</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Immunology Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest Biological Science Journals</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 Immunology, Immunotherapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Omura, Yusuke</au><au>Toiyama, Yuji</au><au>Okugawa, Yoshinaga</au><au>Yin, Chengzeng</au><au>Shigemori, Tsunehiko</au><au>Kusunoki, Kurando</au><au>Kusunoki, Yukina</au><au>Ide, Shozo</au><au>Shimura, Tadanobu</au><au>Fujikawa, Hiroyuki</au><au>Yasuda, Hiromi</au><au>Hiro, Junichiro</au><au>Ohi, Masaki</au><au>Kusunoki, Masato</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Prognostic impacts of tumoral expression and serum levels of PD-L1 and CTLA-4 in colorectal cancer patients</atitle><jtitle>Cancer Immunology, Immunotherapy</jtitle><stitle>Cancer Immunol Immunother</stitle><addtitle>Cancer Immunol Immunother</addtitle><date>2020-12-01</date><risdate>2020</risdate><volume>69</volume><issue>12</issue><spage>2533</spage><epage>2546</epage><pages>2533-2546</pages><issn>0340-7004</issn><eissn>1432-0851</eissn><abstract>Background
Programmed cell death ligand-1 (PD-L1) and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) play a pivotal role in cancer immunotherapy. Each of these molecules has a membrane-bound receptor form (mPD-L1/mCTLA-4) and a soluble form (sPD-L1/sCTLA-4). However, these prognostic impacts in colorectal cancer (CRC) remain unclear.
Methods
We immunohistochemically scored tumoral mPD-L1/mCTLA-4 expression and quantified preoperative circulating sPD-L1/sCTLA-4 levels using matched serum specimens from 131 patients with pStage I–III CRC. We also examined the association between these statuses and tumor infiltrating lymphocytes (TILs) in these patients.
Results
Elevated levels of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 were significantly correlated with poor overall survival (OS) and disease-free survival (DFS). Co-high expression of tumoral mPD-L1 and mCTLA-4 or co-elevated levels of serum sPD-L1 and sCTLA-4 were strongly correlated with poor OS and DFS. Multivariate analysis revealed that both statuses were negative independent prognostic factors for OS [hazard ratio (HR) 3.86, 95% confidence interval (95% CI) 1.71–8.51,
p
= 0.001; HR 5.72, 95% CI 1.87–14.54,
p
= 0.004, respectively] and DFS (HR 2.53, 95% CI 1.23–4.95,
p
= 0.01; HR 6.88, 95% CI 2.42–17.13,
p
= 0.0008, respectively). Although low expression of tumoral mCTLA-4 was significantly correlated with increased CD8(+) TILs, there was no correlation in any other combination.
Conclusions
We verified the prognostic impacts of mPD-L1, mCTLA-4, sPD-L1 and sCTLA-4 in pStage I–III CRC patients. Dual evaluation of immune checkpoint molecules in primary tissues or preoperative serum could identify a patient population with poor prognosis in these patients.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer Berlin Heidelberg</pub><pmid>32577816</pmid><doi>10.1007/s00262-020-02645-1</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0003-1301-3268</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0340-7004 |
| ispartof | Cancer Immunology, Immunotherapy, 2020-12, Vol.69 (12), p.2533-2546 |
| issn | 0340-7004 1432-0851 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_11027465 |
| source | MEDLINE; SpringerLink (Online service); PubMed Central |
| subjects | Adult Aged Aged, 80 and over Apoptosis B7-H1 Antigen - blood B7-H1 Antigen - immunology B7-H1 Antigen - metabolism Biomarkers, Tumor - blood Biomarkers, Tumor - immunology Biomarkers, Tumor - metabolism Cancer Cancer immunotherapy Cancer Research CD8 antigen Cell death Colon - immunology Colon - pathology Colon - surgery Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - blood Colorectal Neoplasms - immunology Colorectal Neoplasms - mortality Colorectal Neoplasms - surgery CTLA-4 Antigen - blood CTLA-4 Antigen - immunology CTLA-4 Antigen - metabolism CTLA-4 protein Cytotoxicity Disease-Free Survival Female Humans Immune checkpoint Immunology Immunotherapy Kaplan-Meier Estimate Lymphocytes T Lymphocytes, Tumor-Infiltrating - immunology Lymphocytes, Tumor-Infiltrating - metabolism Male Medical prognosis Medicine Medicine & Public Health Middle Aged Multivariate analysis Neoplasm Staging Oncology Original Original Article PD-L1 protein Prognosis Rectum - immunology Rectum - pathology Rectum - surgery Retrospective Studies Serum levels |
| title | Prognostic impacts of tumoral expression and serum levels of PD-L1 and CTLA-4 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=2025-01-22T15%3A47%3A41IST&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=Prognostic%20impacts%20of%20tumoral%20expression%20and%20serum%20levels%20of%20PD-L1%20and%20CTLA-4%20in%20colorectal%20cancer%20patients&rft.jtitle=Cancer%20Immunology,%20Immunotherapy&rft.au=Omura,%20Yusuke&rft.date=2020-12-01&rft.volume=69&rft.issue=12&rft.spage=2533&rft.epage=2546&rft.pages=2533-2546&rft.issn=0340-7004&rft.eissn=1432-0851&rft_id=info:doi/10.1007/s00262-020-02645-1&rft_dat=%3Cproquest_pubme%3E2473374864%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=2473374864&rft_id=info:pmid/32577816&rfr_iscdi=true |