T. Ehrlich et al., THE EFFECT OF H-RAS EXPRESSION ON TUMORIGENICITY AND IMMUNOGENICITY OF BALB C 3T3 FIBROBLASTS/, Immunology letters, 39(1), 1993, pp. 3-8
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 w
hile 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 cyto
toxic T cells (CTL) with broad specificity, that lysed all types of Ba
lb/c 3T3 cells tested. Immunization of Balb/c mice with 98/4v cells pr
evented homologous tumor formation and partially inhibited the formati
on 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 cel
ls were important for eliciting in vivo tumor rejection of H-ras + v-m
yc-transfected cells. In contrast, antigens eliciting the cytotoxic T-
cell response, and possibly also the in vivo tumor cell rejection resp
onse, were expressed on all cell types tested but were immunogenic onl
y on the surface of 98/4v cells. We further determined major histocomp
atibility complex (MHC) class-I molecule expression on the outer cell
surface and found that H-2K was down-regulated in H-ras-transfected ce
lls. The results support the observation that oncogenes can down-regul
ate specific MHC antigens, thereby preventing presentation of tumor an
tigens and allowing tumor escape from immune recognition.