NATURAL-KILLER-CELLS AND INTERLEUKIN-12 IN PATIENTS WITH ADVANCED CERVICAL-CANCER UNDER NEOADJUVANT CHEMOTHERAPY

Patients with advanced cervical cancer have deficient natural killer ( NK) cell activity, usually as a consequence of tumor invasion, which r esults in tumor NK cell sequestration. The reason for the occurrence o f such alterations in patients under chemotherapy is unknown. We evalu ated the activity and number of NK cells and T cell subpopulations in ten patients before and three weeks after neoadjuvant chemotherapy (CT ). The schedule used was cis-platinum (100 mg/m(2) per cycle) and bleo mycin (15 mg/cycle), repeated every 28 days. Although there were simil ar levels of NK cells before and after CT in both groups, we observed greater cytotoxicity of peripheral blood lymphocytes and increased lev els of CD4(+) and CD8(+) T cells (P<0.01) in five patients who present ed a good clinical response when compared to the group with a poor res ponse. IL-12, known to increase NK cell activity when added to periphe ral blood lymphocyte cultures, markedly increased lytic activity befor e and after CT only in the group with a good clinical response. These results suggest that NK cells from the poorly responding patient group express less lytic activity per NK cell and are insensitive to IL-12 stimulation, probably as a result of reduced IL-12 receptor expression or a defective intracellular transduction mechanism. The present find ings may be useful as a prognostic factor in clinical practice and als o provide support for human clinical trials of IL-12 and neoadjuvant C T for the treatment of malignant cervical tumors.