Lymphocyte cytotoxicity of patients developing multiple primary melanomas.

A study of cellular immunity was conducted, with particular attention to natural killer cell mediated in vitro cytotoxicity in 6 patients who had two or three primary melanomas (2 patients presenting synchronously with multiple primaries and additional melanomas subsequently developing in 4). All 6 patients were reactive to one or other recall skin test antigens (PPD, streptokinase streptodornase (SK-SD), monilia, mumps) and DNCB skin testing. All exhibited natural killing against melanoma and nomelanoma tumor target cells when examined in the 3H proline microcytotoxicity test with unfractionated as well as natural killer cell enriched (Fc receptor positive cells recovered as Fc receptor rosettes) lymphocyte fractions. None of the 4 patients who subsequently had additional primary tumors was found to lack in mature T or natural killer cell mediated cytotoxicity at the time of the development of additional primaries. Two melanoma cell lines were established from two separate primary tumors in 1 patient and in vitro cytotoxicity assays were performed with that patient's lymphocytes (unfractionated, T enriched, and natural killer cell enriched fractions) against these two lines. While the first melanoma cell line was consistently sensitive to lysis by all three lymphocyte fractions, the other cell line showed no sensitivity either for natural killing or for T enriched lymphocyte mediated lysis at any effector to target ratio. These results suggested that in vitro natural cytotoxicity was not translated into any substantive immunoprotective role in the development of multiple primary tumors and that the two separate melanoma cell lines from the same patient were antigenically hererogenous. Antigenic heterogeneity between different primary tumors may explain the lack of immunity against such development of multiple tumors of the same histology.