Clinical significance and regulation of the costimulatory molecule B7-H1 in pancreatic cancer
Abstract We investigated the expression pattern and clinical significance of the costimulatory ligands B7-1, B7-2, B7-H1, and B7-DC, and their counter-receptors CTLA-4 and PD-1 in pancreatic cancer. Gene expression of all examined costimulatory molecules was significantly upregulated in pancreatic c...
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| Veröffentlicht in: | Cancer letters 2008-09, Vol.268 (1), p.98-109 |
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| container_title | Cancer letters |
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| creator | Loos, Martin Giese, Nathalia A Kleeff, Jörg Giese, Thomas Gaida, Matthias M Bergmann, Frank Laschinger, Melanie W.Büchler, Markus Friess, Helmut |
| description | Abstract We investigated the expression pattern and clinical significance of the costimulatory ligands B7-1, B7-2, B7-H1, and B7-DC, and their counter-receptors CTLA-4 and PD-1 in pancreatic cancer. Gene expression of all examined costimulatory molecules was significantly upregulated in pancreatic cancer tissues. B7-1, B7-2, B7-H1, and B7-DC protein was detectable in pancreatic cancer cells. Only the expression of B7-H1 significantly correlated with postoperative survival ( p < 0.0001). B7-H1 was inducible in cultured pancreatic cancer cells by IFN-γ and significantly correlated with the level of IFN-γ expression in human pancreatic cancer tissues (Spearman ρ = 0.4536, p = 0.0029). B7-H1 positive tumors showed an increased prevalence of tumor-infiltrating regulatory T cells (Tregs ) compared to B7-H1 negative tumors. Among the investigated costimulatory molecules only tumor-associated B7-H1 seems to be of prognostic relevance in pancreatic cancer. B7-H1 might, therefore, be involved in the downregulation of antitumor responses through regulation of Tregs in pancreatic cancer. Our findings also suggest a dual role of IFN-γ in antitumor response. Through induction of B7-H1 in pancreatic cancer cells IFN-γ might contribute to the evasion of antitumor immunity. |
| doi_str_mv | 10.1016/j.canlet.2008.03.056 |
| format | Article |
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Gene expression of all examined costimulatory molecules was significantly upregulated in pancreatic cancer tissues. B7-1, B7-2, B7-H1, and B7-DC protein was detectable in pancreatic cancer cells. Only the expression of B7-H1 significantly correlated with postoperative survival ( p < 0.0001). B7-H1 was inducible in cultured pancreatic cancer cells by IFN-γ and significantly correlated with the level of IFN-γ expression in human pancreatic cancer tissues (Spearman ρ = 0.4536, p = 0.0029). B7-H1 positive tumors showed an increased prevalence of tumor-infiltrating regulatory T cells (Tregs ) compared to B7-H1 negative tumors. Among the investigated costimulatory molecules only tumor-associated B7-H1 seems to be of prognostic relevance in pancreatic cancer. B7-H1 might, therefore, be involved in the downregulation of antitumor responses through regulation of Tregs in pancreatic cancer. Our findings also suggest a dual role of IFN-γ in antitumor response. Through induction of B7-H1 in pancreatic cancer cells IFN-γ might contribute to the evasion of antitumor immunity.</description><identifier>ISSN: 0304-3835</identifier><identifier>EISSN: 1872-7980</identifier><identifier>DOI: 10.1016/j.canlet.2008.03.056</identifier><identifier>PMID: 18486325</identifier><language>eng</language><publisher>Ireland: Elsevier Ireland Ltd</publisher><subject>Antigens, CD - metabolism ; Apoptosis ; B7-1 Antigen - metabolism ; B7-2 Antigen - metabolism ; B7-H1 (PD-L1) ; Cancer therapies ; Cell cycle ; Cell Line, Tumor ; Clinical trials ; Costimulation ; CTLA-4 Antigen ; Cytokines ; Cytokines - metabolism ; Cytotoxicity ; Esophageal cancer ; Gene expression ; Hematology, Oncology and Palliative Medicine ; Humans ; Immune system ; Interferon-gamma - metabolism ; Interferon-γ ; Ligands ; Lymphocytes ; Lymphocytes, Tumor-Infiltrating - immunology ; Medical prognosis ; Medical research ; Mortality ; Pancreatic cancer ; Pancreatic Neoplasms - immunology ; Pancreatic Neoplasms - metabolism ; Pancreatic Neoplasms - mortality ; Programmed Cell Death 1 Ligand 2 Protein ; Studies ; Survival Analysis ; T cell receptors ; T-Lymphocytes, Regulatory - immunology ; Tumors ; Up-Regulation</subject><ispartof>Cancer letters, 2008-09, Vol.268 (1), p.98-109</ispartof><rights>Elsevier Ireland Ltd</rights><rights>2008 Elsevier Ireland Ltd</rights><rights>Copyright Elsevier Limited Sep 8, 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-2ae9356ff0940f7df118ab5fdf1aefdf7252395f8fd007f877a68dfcd4f24dc03</citedby><cites>FETCH-LOGICAL-c540t-2ae9356ff0940f7df118ab5fdf1aefdf7252395f8fd007f877a68dfcd4f24dc03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0304383508002371$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18486325$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Loos, Martin</creatorcontrib><creatorcontrib>Giese, Nathalia A</creatorcontrib><creatorcontrib>Kleeff, Jörg</creatorcontrib><creatorcontrib>Giese, Thomas</creatorcontrib><creatorcontrib>Gaida, Matthias M</creatorcontrib><creatorcontrib>Bergmann, Frank</creatorcontrib><creatorcontrib>Laschinger, Melanie</creatorcontrib><creatorcontrib>W.Büchler, Markus</creatorcontrib><creatorcontrib>Friess, Helmut</creatorcontrib><title>Clinical significance and regulation of the costimulatory molecule B7-H1 in pancreatic cancer</title><title>Cancer letters</title><addtitle>Cancer Lett</addtitle><description>Abstract We investigated the expression pattern and clinical significance of the costimulatory ligands B7-1, B7-2, B7-H1, and B7-DC, and their counter-receptors CTLA-4 and PD-1 in pancreatic cancer. Gene expression of all examined costimulatory molecules was significantly upregulated in pancreatic cancer tissues. B7-1, B7-2, B7-H1, and B7-DC protein was detectable in pancreatic cancer cells. Only the expression of B7-H1 significantly correlated with postoperative survival ( p < 0.0001). B7-H1 was inducible in cultured pancreatic cancer cells by IFN-γ and significantly correlated with the level of IFN-γ expression in human pancreatic cancer tissues (Spearman ρ = 0.4536, p = 0.0029). B7-H1 positive tumors showed an increased prevalence of tumor-infiltrating regulatory T cells (Tregs ) compared to B7-H1 negative tumors. Among the investigated costimulatory molecules only tumor-associated B7-H1 seems to be of prognostic relevance in pancreatic cancer. B7-H1 might, therefore, be involved in the downregulation of antitumor responses through regulation of Tregs in pancreatic cancer. Our findings also suggest a dual role of IFN-γ in antitumor response. Through induction of B7-H1 in pancreatic cancer cells IFN-γ might contribute to the evasion of antitumor immunity.</description><subject>Antigens, CD - metabolism</subject><subject>Apoptosis</subject><subject>B7-1 Antigen - metabolism</subject><subject>B7-2 Antigen - metabolism</subject><subject>B7-H1 (PD-L1)</subject><subject>Cancer therapies</subject><subject>Cell cycle</subject><subject>Cell Line, Tumor</subject><subject>Clinical trials</subject><subject>Costimulation</subject><subject>CTLA-4 Antigen</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Cytotoxicity</subject><subject>Esophageal cancer</subject><subject>Gene expression</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Immune system</subject><subject>Interferon-gamma - metabolism</subject><subject>Interferon-γ</subject><subject>Ligands</subject><subject>Lymphocytes</subject><subject>Lymphocytes, Tumor-Infiltrating - immunology</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Mortality</subject><subject>Pancreatic cancer</subject><subject>Pancreatic Neoplasms - immunology</subject><subject>Pancreatic Neoplasms - metabolism</subject><subject>Pancreatic Neoplasms - mortality</subject><subject>Programmed Cell Death 1 Ligand 2 Protein</subject><subject>Studies</subject><subject>Survival Analysis</subject><subject>T cell receptors</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>Tumors</subject><subject>Up-Regulation</subject><issn>0304-3835</issn><issn>1872-7980</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk-LFDEQxYMo7rj6DUQCgrduK__TF0EHdYUFD-pRQjZdWTP2dI9JtzDf3rQzsLCXvSRF-L0Xql4R8pJBy4Dpt7s2-HHAueUAtgXRgtKPyIZZwxvTWXhMNiBANsIKdUGelbIDACWNekoumJVWC6425Od2SGMKfqAl3Y4p1nIMSP3Y04y3y-DnNI10inT-hTRMZU779XHKR7qfBgzLgPSDaa4YTSM9VG3GKgn0v01-Tp5EPxR8cb4vyY9PH79vr5rrr5-_bN9fN0FJmBvusRNKxwidhGj6yJj1NyrWwmM9DVdcdCra2AOYaI3x2vYx9DJy2QcQl-TNyfeQpz8LltntUwk4DH7EaSlOd8JY3ckHQc5AW61Xx9f3wN205LE24ZiWCkBaziolT1TIUykZozvktPf56Bi4NSW3c6eU3JqSA-FqSlX26my-3OyxvxOdY6nAuxOAdWh_E2ZXQsI60T5lDLPrp_TQD_cNwjnn33jEcteLK9yB-7ZuyrooYAG4MEz8A-u0ud8</recordid><startdate>20080908</startdate><enddate>20080908</enddate><creator>Loos, Martin</creator><creator>Giese, Nathalia A</creator><creator>Kleeff, Jörg</creator><creator>Giese, Thomas</creator><creator>Gaida, Matthias M</creator><creator>Bergmann, Frank</creator><creator>Laschinger, Melanie</creator><creator>W.Büchler, Markus</creator><creator>Friess, Helmut</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Limited</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>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7T5</scope><scope>7X8</scope></search><sort><creationdate>20080908</creationdate><title>Clinical significance and regulation of the costimulatory molecule B7-H1 in pancreatic cancer</title><author>Loos, Martin ; Giese, Nathalia A ; Kleeff, Jörg ; Giese, Thomas ; Gaida, Matthias M ; Bergmann, Frank ; Laschinger, Melanie ; W.Büchler, Markus ; Friess, Helmut</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-2ae9356ff0940f7df118ab5fdf1aefdf7252395f8fd007f877a68dfcd4f24dc03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Antigens, CD - metabolism</topic><topic>Apoptosis</topic><topic>B7-1 Antigen - metabolism</topic><topic>B7-2 Antigen - metabolism</topic><topic>B7-H1 (PD-L1)</topic><topic>Cancer therapies</topic><topic>Cell cycle</topic><topic>Cell Line, Tumor</topic><topic>Clinical trials</topic><topic>Costimulation</topic><topic>CTLA-4 Antigen</topic><topic>Cytokines</topic><topic>Cytokines - metabolism</topic><topic>Cytotoxicity</topic><topic>Esophageal cancer</topic><topic>Gene expression</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Immune system</topic><topic>Interferon-gamma - metabolism</topic><topic>Interferon-γ</topic><topic>Ligands</topic><topic>Lymphocytes</topic><topic>Lymphocytes, Tumor-Infiltrating - immunology</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Mortality</topic><topic>Pancreatic cancer</topic><topic>Pancreatic Neoplasms - immunology</topic><topic>Pancreatic Neoplasms - metabolism</topic><topic>Pancreatic Neoplasms - mortality</topic><topic>Programmed Cell Death 1 Ligand 2 Protein</topic><topic>Studies</topic><topic>Survival Analysis</topic><topic>T cell receptors</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>Tumors</topic><topic>Up-Regulation</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Loos, Martin</creatorcontrib><creatorcontrib>Giese, Nathalia A</creatorcontrib><creatorcontrib>Kleeff, Jörg</creatorcontrib><creatorcontrib>Giese, Thomas</creatorcontrib><creatorcontrib>Gaida, Matthias M</creatorcontrib><creatorcontrib>Bergmann, Frank</creatorcontrib><creatorcontrib>Laschinger, Melanie</creatorcontrib><creatorcontrib>W.Büchler, Markus</creatorcontrib><creatorcontrib>Friess, Helmut</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>Immunology Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cancer letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Loos, Martin</au><au>Giese, Nathalia A</au><au>Kleeff, Jörg</au><au>Giese, Thomas</au><au>Gaida, Matthias M</au><au>Bergmann, Frank</au><au>Laschinger, Melanie</au><au>W.Büchler, Markus</au><au>Friess, Helmut</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical significance and regulation of the costimulatory molecule B7-H1 in pancreatic cancer</atitle><jtitle>Cancer letters</jtitle><addtitle>Cancer Lett</addtitle><date>2008-09-08</date><risdate>2008</risdate><volume>268</volume><issue>1</issue><spage>98</spage><epage>109</epage><pages>98-109</pages><issn>0304-3835</issn><eissn>1872-7980</eissn><abstract>Abstract We investigated the expression pattern and clinical significance of the costimulatory ligands B7-1, B7-2, B7-H1, and B7-DC, and their counter-receptors CTLA-4 and PD-1 in pancreatic cancer. Gene expression of all examined costimulatory molecules was significantly upregulated in pancreatic cancer tissues. B7-1, B7-2, B7-H1, and B7-DC protein was detectable in pancreatic cancer cells. Only the expression of B7-H1 significantly correlated with postoperative survival ( p < 0.0001). B7-H1 was inducible in cultured pancreatic cancer cells by IFN-γ and significantly correlated with the level of IFN-γ expression in human pancreatic cancer tissues (Spearman ρ = 0.4536, p = 0.0029). B7-H1 positive tumors showed an increased prevalence of tumor-infiltrating regulatory T cells (Tregs ) compared to B7-H1 negative tumors. Among the investigated costimulatory molecules only tumor-associated B7-H1 seems to be of prognostic relevance in pancreatic cancer. B7-H1 might, therefore, be involved in the downregulation of antitumor responses through regulation of Tregs in pancreatic cancer. Our findings also suggest a dual role of IFN-γ in antitumor response. Through induction of B7-H1 in pancreatic cancer cells IFN-γ might contribute to the evasion of antitumor immunity.</abstract><cop>Ireland</cop><pub>Elsevier Ireland Ltd</pub><pmid>18486325</pmid><doi>10.1016/j.canlet.2008.03.056</doi><tpages>12</tpages></addata></record> |
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| subjects | Antigens, CD - metabolism Apoptosis B7-1 Antigen - metabolism B7-2 Antigen - metabolism B7-H1 (PD-L1) Cancer therapies Cell cycle Cell Line, Tumor Clinical trials Costimulation CTLA-4 Antigen Cytokines Cytokines - metabolism Cytotoxicity Esophageal cancer Gene expression Hematology, Oncology and Palliative Medicine Humans Immune system Interferon-gamma - metabolism Interferon-γ Ligands Lymphocytes Lymphocytes, Tumor-Infiltrating - immunology Medical prognosis Medical research Mortality Pancreatic cancer Pancreatic Neoplasms - immunology Pancreatic Neoplasms - metabolism Pancreatic Neoplasms - mortality Programmed Cell Death 1 Ligand 2 Protein Studies Survival Analysis T cell receptors T-Lymphocytes, Regulatory - immunology Tumors Up-Regulation |
| title | Clinical significance and regulation of the costimulatory molecule B7-H1 in pancreatic cancer |
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