TY - JOUR
T1 - NY-CO-58/KIF2C is overexpressed in a variety of solid tumors and induces frequent T cell responses in patients with colorectal cancer
AU - Gnjatic, Sacha
AU - Cao, Yanran
AU - Reichelt, Uta
AU - Yekebas, Emre F.
AU - Nölker, Christina
AU - Marx, Andreas H.
AU - Erbersdobler, Andreas
AU - Nishikawa, Hiroyoshi
AU - Hildebrandt, York
AU - Bartels, Katrin
AU - Horn, Christiane
AU - Stahl, Tanja
AU - Gout, Ivan
AU - Filonenko, Valeriy
AU - Ling, Khoon Lin
AU - Cerundolo, Vincenzo
AU - Luetkens, Tim
AU - Ritter, Gerd
AU - Friedrichs, Kay
AU - Leuwer, Rudolf
AU - Hegewisch-Becker, Susanna
AU - Izbicki, Jakob R.
AU - Bokemeyer, Carsten
AU - Old, Lloyd J.
AU - Atanackovic, Djordje
PY - 2010/7/15
Y1 - 2010/7/15
N2 - 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.
AB - 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.
KW - Colorectal cancer
KW - Immunotherapy
KW - T cells
KW - Tumor antigen
KW - Tumor immunology
UR - http://www.scopus.com/inward/record.url?scp=77953719481&partnerID=8YFLogxK
U2 - 10.1002/ijc.25058
DO - 10.1002/ijc.25058
M3 - Article
C2 - 19937794
AN - SCOPUS:77953719481
SN - 0020-7136
VL - 127
SP - 381
EP - 393
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 2
ER -