ENHANCEMENT OF THE ANTITUMOR IMMUNE-RESPONSE USING A COMBINATION OF INTERFERON-GAMMA AND B7 EXPRESSION IN AN EXPERIMENTAL MAMMARY-CARCINOMA

In recent years, tumor immunotherapy has begun to exploit the emerging knowledge of the mechanisms of T cell activation to enhance the immun e responses to tumors. However, many tumors, despite genetic modificat ion to express co-stimulatory molecules or cytokines, are not readily rejected due to their inherently poor immunogenicity. In the present s tudy, we tested whether expression of the costimulatory ligand B7-I an d the immunostimulatory cytokines interferon gamma (IFN-gamma) and gra nulocyte-macrophage colony-stimulating factor (GM-CSF) by a mammary ca rcinoma (SMI) would sufficiently augment its immunogenicity to obtain rejection and immunity. Our findings demonstrate that expression of B7 , IFN-gamma, or GM-CSF alone, or co-expression of B7 and GM-CSF did no t result in rejection of SMI. However, co-expression of B7 and IFN-gam ma was sufficient to result in regression of SMI tumors by a CD8(+) T cell-dependent mechanism. Rejection of the B7/IFN-gamma-expressing SMI tumor resulted in protection from rechallenge not only with the unmod ified SMI tumor but with another syngeneic mammary tumor. Our data sup port the idea that although B7 expression alone may not be sufficient for rejection of certain tumors, the immune system may be stimulated t o mount an effective anti-tumor immune response by the co-expression o f both the co-stimulatory ligand and a cytokine.