Human tankyrases are aberrantly expressed in colon tumors and contain multiple epitopes that induce humoral and cellular immune responses in cancer patients

Purpose Tankyrases 1 and 2 are telomere-associated poly(ADP-ribose) polymerases (PARP) that can positively regulate telomere elongation and interact with multiple cellular proteins. Recent reports implicated tankyrases as tumor antigens and potential targets of anticancer treatment. We examined expr...

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Veröffentlicht in:Cancer Immunology, Immunotherapy Immunotherapy, 2008-06, Vol.57 (6), p.871-881
Hauptverfasser: Shebzukhov, Yuriy V., Lavrik, Inna N., Karbach, Julia, Khlgatian, Svetlana V., Koroleva, Ekaterina P., Belousov, Pavel V., Kashkin, Kirill N., Knuth, Alexander, Jager, Elke, Chi, Nai-Wen, Kuprash, Dmitry V., Nedospasov, Sergei A.
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container_issue 6
container_start_page 871
container_title Cancer Immunology, Immunotherapy
container_volume 57
creator Shebzukhov, Yuriy V.
Lavrik, Inna N.
Karbach, Julia
Khlgatian, Svetlana V.
Koroleva, Ekaterina P.
Belousov, Pavel V.
Kashkin, Kirill N.
Knuth, Alexander
Jager, Elke
Chi, Nai-Wen
Kuprash, Dmitry V.
Nedospasov, Sergei A.
description Purpose Tankyrases 1 and 2 are telomere-associated poly(ADP-ribose) polymerases (PARP) that can positively regulate telomere elongation and interact with multiple cellular proteins. Recent reports implicated tankyrases as tumor antigens and potential targets of anticancer treatment. We examined expression of tankyrases in colon tumors and immune response to these enzymes in patients with different types of cancer. Methods mRNA and protein expression was evaluated by quantitative real-time RT-PCR and Western blotting, respectively. Humoral immune response to recombinant tankyrases was investigated by modified enzyme-linked immunoassays. Cellular immune response was analysed by ELISPOT and 51 Cr release assays. Results We found that both mRNA and protein levels of tankyrase 2 (TNKL) are upregulated in colon tumors. In contrast, protein level of tankyrase 1 (TNKS) is downregulated, while mRNA level shows variable changes. More than a quarter of colon cancer patients develop humoral immune response to at least one of the two tankyrases. In this study we mapped common and unique B-cell epitopes located in different domains of the two proteins. Additionally, we present evidence for T-cell responses both to epitopes that are unique for TNKL and to those shared between TNKL and TNKS. Conclusion Our study favors a biomarker usage of antibody response to tankyrases. Spontaneous CD8 + T-cell responses to these enzymes are rare and further investigation is needed to evaluate tankyrases as potential targets for cancer immunotherapy.
doi_str_mv 10.1007/s00262-007-0423-z
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Recent reports implicated tankyrases as tumor antigens and potential targets of anticancer treatment. We examined expression of tankyrases in colon tumors and immune response to these enzymes in patients with different types of cancer. Methods mRNA and protein expression was evaluated by quantitative real-time RT-PCR and Western blotting, respectively. Humoral immune response to recombinant tankyrases was investigated by modified enzyme-linked immunoassays. Cellular immune response was analysed by ELISPOT and 51 Cr release assays. Results We found that both mRNA and protein levels of tankyrase 2 (TNKL) are upregulated in colon tumors. In contrast, protein level of tankyrase 1 (TNKS) is downregulated, while mRNA level shows variable changes. More than a quarter of colon cancer patients develop humoral immune response to at least one of the two tankyrases. In this study we mapped common and unique B-cell epitopes located in different domains of the two proteins. Additionally, we present evidence for T-cell responses both to epitopes that are unique for TNKL and to those shared between TNKL and TNKS. Conclusion Our study favors a biomarker usage of antibody response to tankyrases. Spontaneous CD8 + T-cell responses to these enzymes are rare and further investigation is needed to evaluate tankyrases as potential targets for cancer immunotherapy.</description><identifier>ISSN: 0340-7004</identifier><identifier>EISSN: 1432-0851</identifier><identifier>DOI: 10.1007/s00262-007-0423-z</identifier><identifier>PMID: 18026951</identifier><identifier>CODEN: CIIMDN</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer-Verlag</publisher><subject>Amino Acid Sequence ; Antibody Formation ; Antigens ; Biomarkers, Tumor - metabolism ; Cancer ; Cancer Research ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - metabolism ; Cell division ; Colon ; Colonic Neoplasms - enzymology ; Colonic Neoplasms - pathology ; Enzymes ; Epitope Mapping - methods ; Epitopes - chemistry ; Humans ; Immunity, Cellular ; Immunology ; Immunotherapy - methods ; Investigations ; Leukemia ; Medicine ; Medicine &amp; Public Health ; Molecular Sequence Data ; Neoplasms - immunology ; Neoplasms - therapy ; Oncology ; Original ; Original Article ; Proteins ; Sequence Homology, Amino Acid ; Serology ; Tankyrases - biosynthesis ; Tankyrases - metabolism ; Telomerase ; Tumors</subject><ispartof>Cancer Immunology, Immunotherapy, 2008-06, Vol.57 (6), p.871-881</ispartof><rights>Springer-Verlag 2007</rights><rights>2008 INIST-CNRS</rights><rights>Springer-Verlag 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c517t-fadf2d323a2c4c346972bed1549e524ba19bc53f14d72d210b6ce137761678dc3</citedby><cites>FETCH-LOGICAL-c517t-fadf2d323a2c4c346972bed1549e524ba19bc53f14d72d210b6ce137761678dc3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11030928/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11030928/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,41488,42557,51319,53791,53793</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=20274192$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18026951$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shebzukhov, Yuriy V.</creatorcontrib><creatorcontrib>Lavrik, Inna N.</creatorcontrib><creatorcontrib>Karbach, Julia</creatorcontrib><creatorcontrib>Khlgatian, Svetlana V.</creatorcontrib><creatorcontrib>Koroleva, Ekaterina P.</creatorcontrib><creatorcontrib>Belousov, Pavel V.</creatorcontrib><creatorcontrib>Kashkin, Kirill N.</creatorcontrib><creatorcontrib>Knuth, Alexander</creatorcontrib><creatorcontrib>Jager, Elke</creatorcontrib><creatorcontrib>Chi, Nai-Wen</creatorcontrib><creatorcontrib>Kuprash, Dmitry V.</creatorcontrib><creatorcontrib>Nedospasov, Sergei A.</creatorcontrib><title>Human tankyrases are aberrantly expressed in colon tumors and contain multiple epitopes that induce humoral and cellular immune responses in cancer patients</title><title>Cancer Immunology, Immunotherapy</title><addtitle>Cancer Immunol Immunother</addtitle><addtitle>Cancer Immunol Immunother</addtitle><description>Purpose Tankyrases 1 and 2 are telomere-associated poly(ADP-ribose) polymerases (PARP) that can positively regulate telomere elongation and interact with multiple cellular proteins. 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Additionally, we present evidence for T-cell responses both to epitopes that are unique for TNKL and to those shared between TNKL and TNKS. Conclusion Our study favors a biomarker usage of antibody response to tankyrases. 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Lavrik, Inna N. ; Karbach, Julia ; Khlgatian, Svetlana V. ; Koroleva, Ekaterina P. ; Belousov, Pavel V. ; Kashkin, Kirill N. ; Knuth, Alexander ; Jager, Elke ; Chi, Nai-Wen ; Kuprash, Dmitry V. ; Nedospasov, Sergei A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c517t-fadf2d323a2c4c346972bed1549e524ba19bc53f14d72d210b6ce137761678dc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Amino Acid Sequence</topic><topic>Antibody Formation</topic><topic>Antigens</topic><topic>Biomarkers, Tumor - metabolism</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>CD8-Positive T-Lymphocytes - immunology</topic><topic>CD8-Positive T-Lymphocytes - metabolism</topic><topic>Cell division</topic><topic>Colon</topic><topic>Colonic Neoplasms - enzymology</topic><topic>Colonic Neoplasms - pathology</topic><topic>Enzymes</topic><topic>Epitope Mapping - methods</topic><topic>Epitopes - chemistry</topic><topic>Humans</topic><topic>Immunity, Cellular</topic><topic>Immunology</topic><topic>Immunotherapy - methods</topic><topic>Investigations</topic><topic>Leukemia</topic><topic>Medicine</topic><topic>Medicine &amp; 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Recent reports implicated tankyrases as tumor antigens and potential targets of anticancer treatment. We examined expression of tankyrases in colon tumors and immune response to these enzymes in patients with different types of cancer. Methods mRNA and protein expression was evaluated by quantitative real-time RT-PCR and Western blotting, respectively. Humoral immune response to recombinant tankyrases was investigated by modified enzyme-linked immunoassays. Cellular immune response was analysed by ELISPOT and 51 Cr release assays. Results We found that both mRNA and protein levels of tankyrase 2 (TNKL) are upregulated in colon tumors. In contrast, protein level of tankyrase 1 (TNKS) is downregulated, while mRNA level shows variable changes. More than a quarter of colon cancer patients develop humoral immune response to at least one of the two tankyrases. In this study we mapped common and unique B-cell epitopes located in different domains of the two proteins. Additionally, we present evidence for T-cell responses both to epitopes that are unique for TNKL and to those shared between TNKL and TNKS. Conclusion Our study favors a biomarker usage of antibody response to tankyrases. Spontaneous CD8 + T-cell responses to these enzymes are rare and further investigation is needed to evaluate tankyrases as potential targets for cancer immunotherapy.</abstract><cop>Berlin/Heidelberg</cop><pub>Springer-Verlag</pub><pmid>18026951</pmid><doi>10.1007/s00262-007-0423-z</doi><tpages>11</tpages></addata></record>
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subjects Amino Acid Sequence
Antibody Formation
Antigens
Biomarkers, Tumor - metabolism
Cancer
Cancer Research
CD8-Positive T-Lymphocytes - immunology
CD8-Positive T-Lymphocytes - metabolism
Cell division
Colon
Colonic Neoplasms - enzymology
Colonic Neoplasms - pathology
Enzymes
Epitope Mapping - methods
Epitopes - chemistry
Humans
Immunity, Cellular
Immunology
Immunotherapy - methods
Investigations
Leukemia
Medicine
Medicine & Public Health
Molecular Sequence Data
Neoplasms - immunology
Neoplasms - therapy
Oncology
Original
Original Article
Proteins
Sequence Homology, Amino Acid
Serology
Tankyrases - biosynthesis
Tankyrases - metabolism
Telomerase
Tumors
title Human tankyrases are aberrantly expressed in colon tumors and contain multiple epitopes that induce humoral and cellular immune responses in cancer patients
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