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Immunology |
Medizinische Klinik III, Hematology, Oncology and Transfusion Medicine [D. N., U. K., A. S., A. L., A. M. A., E. T., C. S.] and Chirurgische Klinik, Surgery [G. B., H-J. B.], University Hospital Benjamin Franklin, Free University Berlin, 12200 Berlin, Germany, and Istituto Nazionale Tumori, 20133 Milan, Italy [L. R.]
The antigens epithelial cell adhesion molecule (Ep-CAM),
her-2/neu, and carcinoembryonic antigen (CEA) are
potential T-cell targets in antigen-specific vaccination-based cancer
therapy. We performed this study to evaluate whether a natural specific
T-cell response against these tumor-associated antigens (TAAs) already
exists in patients with colorectal carcinoma (CRC). We used the IFN-
ELISPOT assay to detect circulating TAA-reactive T cells directly
ex vivo in unstimulated peripheral blood mononuclear
cells. We analyzed the T-cell response in peripheral blood mononuclear
cells of 22 HLA-A2-positive patients with CRC and 8 HLA-A2-positive
healthy subjects against 3 HLA A2-restricted peptide epitopes of the
TAAs Ep-CAM (GLKAGVIAV), her-2/neu (IISAVVGIL), and CEA
(YLSGANLNL). Seven of 22 patients but none of the 8 healthy subjects
had T cells specifically secreting IFN- in response to one to three
of these antigens (n = 4, Ep-CAM;
n = 5, her-2/neu;
n = 6, CEA). In three of the seven
responding patients, TAA-reactive T cells were further characterized by
flow cytometry. In all three patients, the majority of these T cells
have a
CD3+CD8+IFN-+CD69+CD45RA+
phenotype, resembling activated effector-type T cells. T-cell responses
occurred only in patients with metastatic disease (Dukes’ stages C and
D). The results of this study indicate that natural T-cell responses
against TAAs occur in approximately one-half of CRC patients with
involvement of lymph nodes or distant metastases, but not in CRC
patients with disease confined to the intestinum.
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