NY-CO-58/KIF2C is overexpressed in a variety of solid tumors and induces frequent T cell responses in patients with colorectal cancer Journal Article
| Authors: | Gnjatic, S.; Cao, Y.; Reichelt, U.; Yekebas, E. F.; Nölker, C.; Marx, A. H.; Erbersdobler, A.; Nishikawa, H.; Hildebrandt, Y.; Bartels, K.; Horn, C.; Stahl, T.; Gout, I.; Filonenko, V.; Ling, K. L.; Cerundolo, V.; Luetkens, T.; Ritter, G.; Friedrichs, K.; Leuwer, R.; Hegewisch-Becker, S.; Izbicki, J. R.; Bokemeyer, C.; Old, L. J.; Atanackovic, D. |
| Article Title: | NY-CO-58/KIF2C is overexpressed in a variety of solid tumors and induces frequent T cell responses in patients with colorectal cancer |
| Abstract: | NY-CO-58/KIF2C has been identified as a tumor antigen by screening antibody responses in patients with colorectal cancer. However, expression had not consequently been examined, and nothing was known about its ability to induce spontaneous T cell responses, which have been suggested to play a role in the development of colorectal cancer. We analyzed 5 colorectal cancer cell lines, and tumor samples and adjacent healthy tissues from 176 patients with epithelial cancers for the expression of NY-CO-58/KIF2C by RT-PCR and Western Blot. T cell responses of 43 colorectal cancer patients and 35 healthy donors were evaluated by ELISpot following stimulation with 30mer peptides or full-length protein. All cell lines and tumor samples from colorectal cancer patients expressed NY-CO-58/KIF2C on the protein and RNA level, and expression levels correlated strongly with Ki-67 expression (r = 0.69; p = 0.0003). Investigating NY-CO-58/KIF2C-specific T cell responses, CD8+ T cells directed against 1 or more peptides were found in less than 10% of patients, whereas specific CD4+ T cells were detected in close to 50% of patients. These T cells were of high avidity, recognized the naturally processed antigen and secreted IFN-γ and TNF-α. Depletion of CD4+CD25 + T cells before stimulation significantly increased the intensity of the preexisting response. NY-CO-58/KIF2C is significantly overexpressed in colorectal and other epithelial cancers and expression levels correlate with the proliferative activity of the tumor. Importantly, NY-CO-58/KIF2C was able to induce spontaneous CD4+ T cell responses of the Th1-type, which were tightly controlled by peripheral T regulatory cells. © 2009 UICC. |
| Keywords: | adult; controlled study; human tissue; survival rate; unclassified drug; major clinical study; case control study; genetics; case-control studies; solid tumor; comparative study; cancer staging; neoplasm staging; colorectal cancer; t cells; ki 67 antigen; cd8+ t lymphocyte; cell proliferation; t lymphocyte; cd8-positive t-lymphocytes; metabolism; gene overexpression; reverse transcription polymerase chain reaction; cancer cell culture; pathology; tumor antigen; physiology; colorectal neoplasms; enzyme immunoassay; gene expression regulation; immunoenzyme techniques; blotting, western; gene expression regulation, neoplastic; regulatory t lymphocyte; antigen presentation; immunology; correlation analysis; tumor necrosis factor alpha; immunotherapy; gamma interferon; t-lymphocytes, regulatory; reverse transcriptase polymerase chain reaction; colorectal tumor; antibody response; cd4+ t lymphocyte; cd4-positive t-lymphocytes; western blotting; th1 cell; cytokine release; enzyme linked immunospot assay; kinesin; kinesin 2; tumor immunology; kinesin 2c; kif2c protein, human; th1 cells |
| Journal Title: | International Journal of Cancer |
| Volume: | 127 |
| Issue: | 2 |
| ISSN: | 0020-7136 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2010-07-15 |
| Start Page: | 381 |
| End Page: | 393 |
| Language: | English |
| DOI: | 10.1002/ijc.25058 |
| PUBMED: | 19937794 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | --- - "Export Date: 20 April 2011" - "CODEN: IJCNA" - "Source: Scopus" |
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