TRANSPLANTATION ANALYSES OF THE IMMUNOGENICITY OF EPIDERMAL TUMORS GENERATED IN MURINE SKIN 2-STAGE CARCINOGENESIS PROTOCOLS

SSIN mice are very sensitive to tumor promoters in two-stage skin carc inogenesis protocols. It was recently reported that SSIN mice have few er CD8(+) T-cells than other strains of mice and develop a weaker cyto toxic T-cell response upon challenge with an allogeneic tumor transpla nt. The significance of this muted immune response to processes involv ed in two-stage carcinogenesis depends on the immunogenicity of the tu mors generated in such protocols. Although they have low CD8(+) T-cell contents, SSIN rejected a variety of subcutaneously transplanted allo geneic murine tumors. Analyses of the growth of primary papillomas der ived from ated/12-O-tetradecanoylphorbol-13-acetate-promoted SSIN mice and then subcutaneously transplanted into triple-deficient (bg-nu-xid ), athymic nude and immune-competent and immunosuppressed SSIN mice re vealed that few tumors took and tumor takes were not markedly influenc ed by the immunological status of the transplant recipient. Two tumor cell lines (RS1 and RS2) were derived from the transplantation studies and could be passaged in normal SSIN mice (H-2(q) haplotype). Both tu mors were squamous cell carcinomas (SCCs) by the second in vivo passag e and were rejected in allogeneic mice (BALB/c) but grew in FVB/N mice , a strain having the H-2(q) haplotype. Transplantation studies reveal ed that prior exposure to RS1 and RS2 did not prime SSIN mice to rejec t a subsequent tumor challenge. Three primary SCC tumors derived from SSIN mice in a two-stage carcinogenesis protocol also grew when subcut aneously transplanted in SSIN mice and could be serially passaged. Con sequently, the epidermal SCCs that develop in two-stage carcinogenesis protocols appear to be nonimmunogenic. (C) 1997 Wiley-Liss, Inc.