NK cell activity in the presence of IL-12 is a prognostic assay to neoadjuvant chemotherapy in cervical cancer.

OBJECTIVE: Little is known about the impact of neoadjuvant chemotherapy on cell-mediated immunity in patients with advanced cervical cancers. PATIENTS AND METHODS: We have studied 24 patients with advanced cervical cancer submitted to neoadjuvant chemotherapy (CT) using cis-platinum (100 mg/m(2)/cycle) and bleomycin (30 mg/cycle). The cell-mediated immunity parameters available before and after CT were NK cells, CD4(+)/CD28 and CD8(+)/CD28 T-lymphocyte numbers, PBMC cytotoxicity, and modification of this parameter with "in vitro" addition of IL-12. RESULTS: The number of NK cells was higher before CT (P < 0.008) in 13 patients who presented a good clinical response to treatment, compared to 11 patients with a poor clinical response. In addition, PBMC cytotoxicity (P < 0.001), CD4(+) and CD8(+) T-lymphocyte values (P < 0.0047), and CD8(+)/CD28(+) cells were also higher in the group with a good response compared with the group with a poor response. Addition of IL-12 to the medium increased the lytic capacity of PBMC after CT only in the group with a good clinical response (P < 0.05). CONCLUSIONS: NK cell numbers, CD8(+) T-cell levels, and CD8(+)/CD28(+) cell levels can be used as prognostic factors before CT. Our results suggest that patients with a poor response have lower lytic activity per NK cell and are refractory to IL-12 stimulation, probably as a result of the reduced expression of IL-12 receptors or of an intracellular defect in the mechanism of transduction. These observations also provide support for human clinical trials of IL-12 and neoadjuvant CT in patients with cervical cancer.