T cell responses in colorectal cancer patients: Evidence for class IIHLA-restricted recognition of shared tumor-associated antigens

Few cases of anti-colon cancer specific T lymphocytes have been described s o far. Moreover, the majority of these effecters were generated in vitro by stimulating PBMC from patients or healthy donors with peptides that were d erived from proteins expressed and/or secreted by colon cancer tissue such as CEA, Mucin or Her-2/neu, The aim of our study was to evaluate the immuno genicity of colorectal carcinomas in an autologous setting. We exploited th e antigen processing and presentation capacity of dendritic cells (DC) to e stablish an in vitro autologous system that can bypass the need of obtainin g cultured tumor cells. DC were generated from the adherent monocyte fracti on of PBMC taken from stage II/III colorectal cancer patients, A single cel l suspension was prepared by mechanical and enzymatic disruption of the sur gical specimens immediately after resection. DC were loaded with autologous tumor lysate, obtained by repeated freezing and thawing, before being used as stimulators for autologous PBL, HLA-class II restricted T cells that re cognize the autologous tumor could be generated in a proportion of patients , The fine specificity of the anti-tumor T cells indicates that differentia tion as well as tumor restricted antigens are expressed in colon cancer and that these antigens can evoke a class II HLA-restricted response in an aut ologous setting, Altogether these findings may open a new perspective for a DC based vaccination of colon cancer patients, Int. J. Cancer 88:956-961, 2000, (C) 2000 Wiley-Liss, Inc.