NY-CO-58/KIF2C is overexpressed in a variety of solid tumors and induces frequent T cell responses in patients with colorectal cancer.
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-gamma and TNF-alpha. 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.
Gnjatic
Sacha
S
Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. gnjatics@mskcc.org
Cao
Yanran
Y
Reichelt
Uta
U
Yekebas
Emre F
EF
Nölker
Christina
C
Marx
Andreas H
AH
Erbersdobler
Andreas
A
Nishikawa
Hiroyoshi
H
Hildebrandt
York
Y
Bartels
Katrin
K
Horn
Christiane
C
Stahl
Tanja
T
Gout
Ivan
I
Filonenko
Valeriy
V
Ling
Khoon-Lin
KL
Cerundolo
Vincenzo
V
Luetkens
Tim
T
Ritter
Gerd
G
Friedrichs
Kay
K
Leuwer
Rudolf
R
Hegewisch-Becker
Susanna
S
Izbicki
Jakob R
JR
Bokemeyer
Carsten
C
Old
Lloyd J
LJ
Atanackovic
Djordje
D
D015153:Blotting, Western; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007124:Immunoenzyme Techniques; D016547:Kinesins / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology
C091489:KIF2C protein, human; D016547:Kinesins