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Local Tumor Control following Single Dose Irradiation of Human Melanoma Xenografts: Relationship to Cellular Radiosensitivity and Influence of an Immune Response by the Athymic Mouse¹

Institute for Cancer Research and The Norwegian Cancer Society, The Norwegian Radium Hospital, Montebello, 0310 Oslo 3, Norway

The potential usefulness of untreated congenitally athymic adult mice as hosts for human tumors in radiocurability studies was investigated using five human melanoma xenograft lines (E.E., E.F., G.E., M.F., V.N.). The tumor radiocurability was found to differ considerably among the lines; the radiation doses required to achieve local control of 50% of the tumors irradiated (TCD₅₀ values) ranged from 29.6 ± 2.1 (SE) to 67.9 ± 3.5 Gy. Since the clinical relevance of experimentally determined TCD₅₀ values depends on to what extent they are modified by a host immune response, a possible immune reactivity against the melanomas was investigated by comparing the radiocurability data with cell survival data measured in vitro after irradiation in vivo and by performing quantitative tumor transplantability studies. The radiocurability and the cell survival data were found to agree well for the E.F., G.E., and M.F. melanomas. Moreover, the number of tumor cells required to achieve tumors in 50% of the inoculation sites (TD₅₀ values) in untreated and in whole-body irradiated mice were similar, suggesting that the TCD₅₀ values measured for these lines were not significantly influenced by a host immune response. On the other hand, the E.E. and V.N. melanomas showed significantly lower TCD₅₀ values in vivo than predicted theoretically from the in vitro cell survival data and a significantly lower number of tumor cells required to achieve tumors in 50% of the inoculation sites in whole-body irradiated than in untreated mice, suggesting that the radiocurability of these two lines was enhanced due to an immune response by the host. Athymic mice may thus express a significant immune reactivity against some human tumor xenograft lines but not against others. Consequently, TCD₅₀ values measured for human tumors in athymic mice cannot be considered to be clinically relevant unless it has been verified that the tumors are not exposed to an immune reaction in the untreated host or the host has been rendered immunologically blank by immunosuppressive treatment.

¹ Financial support was received from The Norwegian Cancer Society, The Norwegian Research Council for Science and the Humanities, and the Nansen Scientific Fund.

² To whom requests for reprints should be addressed, at Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, 0310 Oslo 3, Norway.

Received 11/ 8/88. Revised 2/24/89. Accepted 3/ 7/89.

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