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.
Bibliographical noteFunding Information:
This work was supported,i n part, by grants from Selma and Melvin Maisel and Raquel and Jacobo Gurvitz, Israel Ministry of Health, Israel Cancer Association,I srael Academy of Sciences and Humanities,G erman-IsraelFi oundationfor Scientific Research and Developmentt,h e Israel Cancer Research Fund Career Development Award (N.I.) and a fellowship from the Hista-drut, The General Federationo f Labor in Israel (T.E.).
- Major histocompatibility complex class-I molecule
- Tumor-associated antigens
ASJC Scopus subject areas
- Immunology and Allergy