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01.06.2008 | Original Article

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

verfasst von: 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

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 6/2008

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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.

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Titel: Human tankyrases are aberrantly expressed in colon tumors and contain multiple epitopes that induce humoral and cellular immune responses in cancer patients
verfasst von: 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
Publikationsdatum: 01.06.2008
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 6/2008
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-007-0423-z

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Springer Medizin

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