T cell responses in colorectal cancer patients: evidence for class II HLA-restricted recognition of shared tumor-associated antigens.
Few cases of anti-colon cancer specific T lymphocytes have been described so far. Moreover, the majority of these effectors were generated in vitro by stimulating PBMC from patients or healthy donors with peptides that were derived 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 immunogenicity of colorectal carcinomas in an autologous setting. We exploited the antigen processing and presentation capacity of dendritic cells (DC) to establish an in vitro autologous system that can bypass the need of obtaining cultured tumor cells. DC were generated from the adherent monocyte fraction of PBMC taken from stage II/III colorectal cancer patients. A single cell suspension was prepared by mechanical and enzymatic disruption of the surgical 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 recognize the autologous tumor could be generated in a proportion of patients. The fine specificity of the anti-tumor T cells indicates that differentiation 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 autologous setting. Altogether these findings may open a new perspective for a DC based vaccination of colon cancer patients.
Bremers
A J
AJ
Unit of Immunotherapy of Human Tumors, Istituto Nazionale Tumori, Milano, Italy.
Andreola
S
S
Leo
E
E
Gallino
F
F
Rini
F
F
Lombardo
C
C
Belli
F
F
Kuppen
P J
PJ
Parmiani
G
G
Castelli
C
C
D000951:Antigens, Neoplasm / Q000276:immunology*; D015179:Colorectal Neoplasms / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D013601:T-Lymphocytes / Q000276:immunology*
D000951:Antigens, Neoplasm; D018984:Epitopes, T-Lymphocyte; D000949:Histocompatibility Antigens Class II