Low natural cytotoxicity of peripheral blood mononuclear cells in individuals with high familial incidences of cancer.

The possible role that natural cell-mediated cytotoxicity may play as a host defense mechanism against malignant tumors was investigated. We measured natural cell-mediated cytotoxicity (51Chromium released) in 79 normal individuals using K562 leukemia cells as targets in quadruplicate assays after 3, 4, and 5 hr of incubation using three different effector:target cell ratios (6.2:1, 25:1, and 50:1). Natural cell-mediated cytotoxicity was significantly lower (p less than 0.005) in each of the nine separate assay conditions for individuals with a high familial incidence of cancer compared to individuals with a low incidence of cancer. Moreover, natural cell-mediated cytotoxicity inversely correlated with the number of family members with cancer. The relationship between high familial cancer incidence and low natural cell-mediated cytotoxicity was observed in males as well as in females and in nonsmokers as well as in smokers. The same conclusion was reached whether the data were expressed as percentage of 51Chromium released, as lytic units per 10(7) mononuclear cells, or as lytic units per ml of peripheral blood. Thus, defects in natural cell-mediated cytotoxicity may play a role in the initial stages of human tumorigenesis. It may also be possible to identify individuals at increased risk of cancer development.