THE EFFECT OF H-RAS EXPRESSION ON TUMORIGENICITY AND IMMUNOGENICITY OF BALB/C 3T3 FIBROBLASTS

In an attempt to define immunological parameters affected by the H-ras oncogene, we have used Balb/c 3T3 cells transfected with either H-ras (98/6), H-ras + v-myc (98/4v) or plasmid only (98/1). We found that while control and oncogene-transfected Balb/c 3T3 cells exhibit similar low sensitivity to lysis by natural killer (NK) cells, H-ras + v-myc-transfected cells could immunize syngeneic Balb/c mice and induce cytotoxic T cells (CTL) with broad specificity, that lysed all types of Balb/c 3T3 cells tested. Immunization of Balb/c mice with 98/4v cells prevented homologous tumor formation and partially inhibited the formation of tumors derived from H-ras-transfected cells. 98/6 cells were not immunogenic in vivo and did not protect the animals from a challenge of 98/6 cells. The results suggested that CTLs but not NK effector cells were important for eliciting in vivo tumor rejection of H-ras + v-myc-transfected cells. In contrast, antigens eliciting the cytotoxic T-cell response, and possibly also the in vivo tumor cell rejection response, were expressed on all cell types tested but were immunogenic only on the surface of 98/4v cells. We further determined major histocompatibility complex (MHC) class-I molecule expression on the outer cell surface and found that H-2K was down-regulated in H-ras-transfected cells. The results support the observation that oncogenes can down-regulate specific MHC antigens, thereby preventing presentation of tumor antigens and allowing tumor escape from immune recognition.