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.
Ehrlich
T
T
Department of Microbiology and Immunology, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer-Sheva, Israel.
Wishniak
O
O
Isakov
N
N
Cohen
O
O
Segal
S
S
Rager-Zisman
B
B
Gopas
J
J
D016475:3T3 Cells; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006183:H-2 Antigens / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D016130:Immunophenotyping; D007694:Killer Cells, Natural / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000276:immunology*; D016274:Oncogene Protein p55(v-myc) / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection / Q000235:genetics
D006183:H-2 Antigens; D015395:Histocompatibility Antigens Class I; D016274:Oncogene Protein p55(v-myc); D015689:Oncogene Protein p21(ras)