NY-CO-58/KIF2C is overexpressed in a variety of solid tumors and induces frequent T cell responses in patients with colorectal cancer.
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NY-CO-58/KIF2C is overexpressed in a variety of solid tumors and induces frequent T cell responses in patients with colorectal cancer. / Gnjatic, Sacha; Cao, Yanran; Reichelt, Uta; Yekebas, Emre F.; Nölker, Christina; Marx, Andreas; Erbersdobler, Andreas; Nishikawa, Hiroyoshi; Hildebrandt, York; Bartels, Katrin; Horn, Christiane; Stahl, Tanja; Gout, Ivan; Filonenko, Valeriy; Ling, Khoon-Lin; Cerundolo, Vincenzo; Luetkens, Tim; Ritter, Gerd; Friedrichs, Kay; Leuwer, Rudolf; Hegewisch-Becker, Susanna; Izbicki, Jakob R.; Bokemeyer, Carsten; Old, Lloyd J; Atanackovic, Djordje.
in: INT J CANCER, 2009.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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
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 - 2009
Y1 - 2009
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(+) cells directed against one 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-gamma and TNF-alpha. Depletion of CD4(+)CD25(+) T cells before stimulation significantly increased the intensity of the pre-existing 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. (c) 2009 UICC.
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(+) cells directed against one 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-gamma and TNF-alpha. Depletion of CD4(+)CD25(+) T cells before stimulation significantly increased the intensity of the pre-existing 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. (c) 2009 UICC.
M3 - SCORING: Zeitschriftenaufsatz
JO - INT J CANCER
JF - INT J CANCER
SN - 0020-7136
ER -
