Expression of B7 co-stimulatory molecules by B16 melanoma results in a natural killer cell-dependent local anti-tumour response, but induces T-cell-dependent systemic immunity only against B7-expressing tumours.
In an attempt to enhance the anti-tumour immune response, the co-stimulatory molecules B7-1 or B7-2 were expressed on the surface of B16 melanoma cells. B7-expressing tumours grew more slowly in both syngeneic immunocompetent mice and athymic T cell-immunodeficient nude mice. The delay in growth of B7-expressing tumours was dependent on natural killer (NK) cells, as reductions in tumour growth rates were minimized in mice depleted of NK cells. Systemic immunity to B16 melanoma was examined by vaccination with irradiated tumour cells. Inoculation with irradiated B16 B7-1 cells failed to protect against a subsequent challenge with live parental B16 cells, but conferred partial protection against challenge with live B16 B7-1 cells. In contrast to the local anti-tumour reaction, this protective response was dependent on T cells. The results presented here reveal some of the mechanisms involved in the in vivo response to a poorly immunogenic tumour modified to express co-stimulatory molecules.
Chong
H
H
Department of Histopathology, United Medical and Dental Schools of Guy's and St. Thomas's Hospitals, London, UK.
Hutchinson
G
G
Hart
I R
IR
Vile
R G
RG
D000818:Animals; D000906:Antibodies; D015703:Antigens, CD / Q000276:immunology*; D018122:B7-1 Antigen / Q000276:immunology*; D051940:B7-2 Antigen; D005677:G(M1) Ganglioside / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D008212:Lymphocyte Depletion; D008545:Melanoma / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D000906:Antibodies; D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497965:Cd86 protein, mouse; D008562:Membrane Glycoproteins; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside