There is increasing evidence that tumors elicit specific T-cell responses in a substantial proportion of patients. Recently, we have shown that in patients with colorectal cancer specific T cells against the tumor-associated antigens (TAA) Ep-CAM, her-2/neu or CEA can be detected in peripheral blood using IFN␥-ELISPOT assay. In our study, we have analyzed T-cell responses against HLA-A*0201-restricted epitopes of these TAA in peripheral blood of patients with breast cancer and colorectal cancer. Surprisingly, a complete absence of ex vivo T-cell responses against these TAA was found in 20 patients with breast cancer. In contrast, specific T cells were detectable in 12 of 49 patients with colorectal cancer against at least 1 of these TAA, confirming our previous results. T-cell responses against influenza-derived peptides were similar in both malignancies. The results of our study indicate a difference either of tumor immunogenicity or of the migratory pattern of tumor-specific T cells between breast cancer and colorectal cancer patients. The findings reported here have implications for the development of antigen-specific T-cell therapies. © 2003 Wiley-Liss, Inc.
Key words: breast cancer; colorectal cancer; ELISPOT assay; T-cell response; tumor-associated antigenThe existence of tumor-reactive T cells has been shown for various adenocarcinomas including colorectal (CRC), lung and breast cancer (BC). 1-4 These tumor-reactive T cells derived from peripheral blood or tumor have, however, been detected after in vitro expansion by repeated stimulation with antigen and IL-2. More recently, functional ex vivo analyses have been performed in CRC showing that a proportion of patients spontaneously mount specific CD8ϩ T-cell responses against tumor-associated antigens (TAA) including Ep-CAM, her-2/neu or CEA. 5,6 It is not clear yet whether patients with other adenocarcinomas expressing the same antigens possess similar T-cell responses in peripheral blood. A recent study in breast cancer showed that tumor-reactive T cells can be expanded in the majority of patients from bone marrow but not from blood samples; however, no ex vivo functional analysis of tumor antigen-reactive T cells has been performed. 7 The aim of our study was to analyze T-cell responses against the TAA EpCAM, her-2/neu and CEA in peripheral blood of patients with BC and to compare it with T-cell reactivity found in CRC. To study functional T-cell responses directly ex vivo, we have used the IFN␥-ELISPOT assay detecting specific T cells by their antigeninduced secretion of IFN␥. 8 Ep-CAM (epithelial cell adhesion molecule, 17-1A, EGP-2, GA733-2) is a cell surface glycoprotein that is expressed in more than 90% of CRC and BC tissues, respectively. 9 -12 The incidence of her-2/neu overexpression in CRC and BC is also at comparable levels (about 40% of CRC and 30% of BC). [13][14][15][16][17] Her-2/neu was first identified as a target of cytotoxic T-cell lines in patients with breast and ovarian cancer. 18,19 Using tetramers her-2/neu (369 -377) specific T ...