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-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.
authors: Ludwig Institute for Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. gnjatics@mskcc.org
authors: Sacha
authors: S
authors: Gnjatic
authors: Yanran
authors: Y
authors: Cao
authors: Uta
authors: U
authors: Reichelt
authors: Emre F
authors: EF
authors: Yekebas
authors: Christina
authors: C
authors: Nölker
authors: Andreas H
authors: AH
authors: Marx
authors: Andreas
authors: A
authors: Erbersdobler
authors: Hiroyoshi
authors: H
authors: Nishikawa
authors: York
authors: Y
authors: Hildebrandt
authors: Katrin
authors: K
authors: Bartels
authors: Christiane
authors: C
authors: Horn
authors: Tanja
authors: T
authors: Stahl
authors: Ivan
authors: I
authors: Gout
authors: Valeriy
authors: V
authors: Filonenko
authors: Khoon-Lin
authors: KL
authors: Ling
authors: Vincenzo
authors: V
authors: Cerundolo
authors: Tim
authors: T
authors: Luetkens
authors: Gerd
authors: G
authors: Ritter
authors: Kay
authors: K
authors: Friedrichs
authors: Rudolf
authors: R
authors: Leuwer
authors: Susanna
authors: S
authors: Hegewisch-Becker
authors: Jakob R
authors: JR
authors: Izbicki
authors: Carsten
authors: C
authors: Bokemeyer
authors: Lloyd J
authors: LJ
authors: Old
authors: Djordje
authors: D
authors: Atanackovic
mesh_terms: 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
chemical_list: C091489:KIF2C protein, human; D016547:Kinesins