EXPRESSION OF B7 COSTIMULATORY MOLECULES BY B16 MELANOMA RESULTS IN ANATURAL-KILLER CELL-DEPENDENT LOCAL ANTITUMOR RESPONSE, BUT INDUCES T-CELL-DEPENDENT SYSTEMIC IMMUNITY ONLY AGAINST B7-EXPRESSING TUMORS

In an attempt to enhance the anti-tumour immune response, the co-stimu latory molecules B7-1 or B7-2 were expressed on the surface of B16 mel anoma 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 kil ler (NK) cells, as reductions in tumour growth rates were minimized in mice depleted of NK cells. Systemic immunity to B16 melanoma was exam ined by vaccination with irradiated tumour cells. inoculation with irr adiated B16 B7-1 cells failed to protect against a subsequent challeng e with live parental B16 cells, but conferred partial protection again st challenge with live B16 B7-1 cells. In contrast to the local anti-t umour 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.