Development of immunogenic colorectal cancer cell lines for vaccination: expression of CD80 (B7.1) is not sufficient to restore impaired primary T cell activation in vitro.
The capacity of colorectal carcinoma and melanoma cell lines to induce primary versus effector T lymphocyte activation in vitro was investigated. Established epithelial tumour cell lines derived from colorectal carcinoma and melanoma did not activate a primary proliferative response of resting T lymphocytes in allogeneic mixed lymphocyte tumour cell cultures (MLTCs). In contrast, the same tumour cells were effectively lysed by preactivated cytolytic T cell clones. This demonstrates that tumour cells are impaired in inducing a primary immune response but are susceptible to effector immune responses. Attempts at improving primary T cell activation revealed that exogenous cytokines, including interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2), were not effective. Expression of CD80 (B7.1), by transfecting a CD80 cDNA into the melanoma cell line SkMel63, improved T cell proliferation considerably. In contrast, CD80 expression in two colorectal carcinoma cell lines (SW480, SW707) did not result in T cell activation. This was not due to lack of class II MHC expression on SW480 since coexpression of a HLA-DR3 alloantigen and CD80 had no effect. Our data suggest that de novo CD80 expression is not, in general, sufficient to improve primary T cell activation by human tumour cells.
Habicht
A
A
Angewandte Immunologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
Lindauer
M
M
Galmbacher
P
P
Rudy
W
W
Gebert
J
J
Schackert
H K
HK
Meuer
S C
SC
Moebius
U
U
D000951:Antigens, Neoplasm / Q000032:analysis; D018122:B7-1 Antigen / Q000235:genetics / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000502:physiology; D018014:Gene Transfer Techniques; D005796:Genes; D015803:HLA-DR3 Antigen / Q000235:genetics / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D007959:Lymphocyte Culture Test, Mixed; D008545:Melanoma / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology
D000951:Antigens, Neoplasm; D018122:B7-1 Antigen; D016207:Cytokines; D015803:HLA-DR3 Antigen