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


CONCLUSIONS
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.
Shebzukhov
Yuriy V
YV
Department of Molecular Immunology, Belozersky Institute of Physico-Chemical Biology, Moscow State University, Vorobjovy Gory, Moscow 119899, Russia.
Lavrik
Inna N
IN
Karbach
Julia
J
Khlgatian
Svetlana V
SV
Koroleva
Ekaterina P
EP
Belousov
Pavel V
PV
Kashkin
Kirill N
KN
Knuth
Alexander
A
Jager
Elke
E
Chi
Nai-Wen
NW
Kuprash
Dmitry V
DV
Nedospasov
Sergei A
SA
D000595:Amino Acid Sequence; D000917:Antibody Formation; D014408:Biomarkers, Tumor / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D018604:Epitope Mapping / Q000379:methods; D000939:Epitopes / Q000737:chemistry; D006801:Humans; D007111:Immunity, Cellular; D007167:Immunotherapy / Q000379:methods*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000276:immunology* / Q000628:therapy*; D017386:Sequence Homology, Amino Acid; D038501:Tankyrases / Q000096:biosynthesis* / Q000378:metabolism
D014408:Biomarkers, Tumor; D000939:Epitopes; D038501:Tankyrases; C437334:TNKS2 protein, human; C418109:TNKS protein, human