Spontaneous <i>in vitro</i> cytotoxicity against autochthonous human melanoma cells.

Abstract

Abstract We have examined spontaneous in vitro cytotoxicity mediated by undifferentiated lymphocytes (Ly), mature T cells, and natural killer (NK) cells in 28 patients with malignant melanoma against autochthonous melanoma cells through the 48 hr 3H proline microcytotoxicity assay. Three out of 28 patients have been found to exhibit spontaneous cytotoxicity against autochthonous target cells whereas 26 out of 28 patients are found readily capable of destroying allogeneic melanoma cells and/or sarcoma cells. The difference between autochthonous vs allogeneic cytotoxic reactivity by undifferentiated Ly is significant (p &amp;lt; 0.001). The spontaneous cytotoxicity appears to be detectable in the mature T cell fractions as well as in the Fc receptor bearing “NK cell” fractions derived from patients who exhibit cytotoxicity against autochthonous or allogeneic target cells. On the other hand, the lack of cytotoxicity, seen with unfractionated lymphocytes against autochthonous target cells, is also seen with mature T cells and the Fc receptor bearing NK cells. The same lymphocyte fractions, however, readily exhibit spontaneous cytotoxicity against allogeneic target cells. The striking lack of cytotoxicity against autochthonous melanoma cells raises questions on the potential immunosurveillance role of spontaneous cytotoxicity against cancer development. The lack of such autochthonous cytotoxic reactivity by NK cells may be explained by the fact that spontaneously arising autochthonous cancer cells may not express antigenic determinants that are recognized by NK cells or that such cancer cells may circumvent the natural cytotoxic process by a yet unknown way.