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

Yuriy V. Shebzukhov; Inna N. Lavrik; Julia Karbach; Svetlana V. Khlgatian; Ekaterina P. Koroleva; Pavel V. Belousov; Kirill N. Kashkin; Alexander Knuth; Elke Jager; Nai Wen Chi; Dmitry V. Kuprash; Sergei A. Nedospasov

doi:10.1007/s00262-007-0423-z

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

Yuriy V. Shebzukhov, Inna N. Lavrik, Julia Karbach, Svetlana V. Khlgatian, Ekaterina P. Koroleva, Pavel V. Belousov, Kirill N. Kashkin, Alexander Knuth, Elke Jager, Nai Wen Chi, Dmitry V. Kuprash, Sergei A. Nedospasov

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

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 ⁵¹Cr 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.

Original language	English (US)
Pages (from-to)	871-881
Number of pages	11
Journal	Cancer Immunology, Immunotherapy
Volume	57
Issue number	6
DOIs	https://doi.org/10.1007/s00262-007-0423-z
State	Published - Jun 2008
Externally published	Yes

Keywords

Epitope mapping
SEREX
Telomerase-interacting proteins

ASJC Scopus subject areas

Oncology
Cancer Research
Immunology and Allergy
Immunology

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Shebzukhov, Y. V., Lavrik, I. N., Karbach, J., Khlgatian, S. V., Koroleva, E. P., Belousov, P. V., Kashkin, K. N., Knuth, A., Jager, E., Chi, N. W., Kuprash, D. V., & Nedospasov, S. A. (2008). Human tankyrases are aberrantly expressed in colon tumors and contain multiple epitopes that induce humoral and cellular immune responses in cancer patients. Cancer Immunology, Immunotherapy, 57(6), 871-881. https://doi.org/10.1007/s00262-007-0423-z

Shebzukhov, YV, Lavrik, IN, Karbach, J, Khlgatian, SV, Koroleva, EP, Belousov, PV, Kashkin, KN, Knuth, A, Jager, E, Chi, NW, Kuprash, DV & Nedospasov, SA 2008, 'Human tankyrases are aberrantly expressed in colon tumors and contain multiple epitopes that induce humoral and cellular immune responses in cancer patients', Cancer Immunology, Immunotherapy, vol. 57, no. 6, pp. 871-881. https://doi.org/10.1007/s00262-007-0423-z

@article{2e0093e653164c92985483b93902d53b,

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

abstract = "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 51Cr 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.",

keywords = "Epitope mapping, SEREX, Telomerase-interacting proteins",

author = "Shebzukhov, {Yuriy V.} and Lavrik, {Inna N.} and Julia Karbach and Khlgatian, {Svetlana V.} and Koroleva, {Ekaterina P.} and Belousov, {Pavel V.} and Kashkin, {Kirill N.} and Alexander Knuth and Elke Jager and Chi, {Nai Wen} and Kuprash, {Dmitry V.} and Nedospasov, {Sergei A.}",

note = "Funding Information: Acknowledgments This study was supported by the Ludwig Institute for Cancer Research (New York), by the Cancer Antigen Discovery Collaborative of the Cancer Research Institute, Cancer Research Institute, by Deutsche Forschungsgemeinschaft Grant SFB 633, by grants from the Russian Academy of Sciences (Molecular and Cellular Biology; Medicine) and by Russian Foundation for Basic Research (grant 05-04-49075-a). We are greatly indebted to H.-G. Rammensee and M. Lagarkova for advise and to L.J. Old and A.M. Malyguine for stimulating discussions. We thank O.V. Gurova, A.A. Meshcheryakov and M.R. Lichinitser for providing clinical samples, D. Liepinsh, P. Lemansky and S. Durum for critical reading and valuable comments on the manuscript and T. Kadachigova and R. Kazaryan for assistance.",

year = "2008",

month = jun,

doi = "10.1007/s00262-007-0423-z",

language = "English (US)",

volume = "57",

pages = "871--881",

journal = "Cancer Immunology, Immunotherapy",

issn = "0340-7004",

publisher = "Springer Science and Business Media Deutschland GmbH",

number = "6",

}

TY - JOUR

T1 - Human tankyrases are aberrantly expressed in colon tumors and contain multiple epitopes that induce humoral and cellular immune responses in cancer patients

AU - Shebzukhov, Yuriy V.

AU - Lavrik, Inna N.

AU - Karbach, Julia

AU - Khlgatian, Svetlana V.

AU - Koroleva, Ekaterina P.

AU - Belousov, Pavel V.

AU - Kashkin, Kirill N.

AU - Knuth, Alexander

AU - Jager, Elke

AU - Chi, Nai Wen

AU - Kuprash, Dmitry V.

AU - Nedospasov, Sergei A.

N1 - Funding Information: Acknowledgments This study was supported by the Ludwig Institute for Cancer Research (New York), by the Cancer Antigen Discovery Collaborative of the Cancer Research Institute, Cancer Research Institute, by Deutsche Forschungsgemeinschaft Grant SFB 633, by grants from the Russian Academy of Sciences (Molecular and Cellular Biology; Medicine) and by Russian Foundation for Basic Research (grant 05-04-49075-a). We are greatly indebted to H.-G. Rammensee and M. Lagarkova for advise and to L.J. Old and A.M. Malyguine for stimulating discussions. We thank O.V. Gurova, A.A. Meshcheryakov and M.R. Lichinitser for providing clinical samples, D. Liepinsh, P. Lemansky and S. Durum for critical reading and valuable comments on the manuscript and T. Kadachigova and R. Kazaryan for assistance.

PY - 2008/6

Y1 - 2008/6

N2 - 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 51Cr 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.

AB - 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 51Cr 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.

KW - Epitope mapping

KW - SEREX

KW - Telomerase-interacting proteins

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U2 - 10.1007/s00262-007-0423-z

DO - 10.1007/s00262-007-0423-z

M3 - Article

C2 - 18026951

AN - SCOPUS:43349092644

SN - 0340-7004

VL - 57

SP - 871

EP - 881

JO - Cancer Immunology, Immunotherapy

JF - Cancer Immunology, Immunotherapy

IS - 6

ER -

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

Abstract

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