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 ca ncer submitted to neoadjuvant chemotherapy (CT) using cia-platinum (100 mg/ m(2)/cycle) and bleomycin (30 mg/cycle). The cell-mediated immunity paramet ers available before and after CT were NK cells, CD4(+)/CD28 and CD8(+)/CD2 8 T-lymphocyte numbers, PBMC cytotoxicity, and modification of this paramet er with "in vitro" addition of IL-12, Results. The number of NK cells was higher before CT (P < 0.008) in 13 pati ents who presented a good clinical response to treatment, compared to 11 pa tients 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 t he group with a poor response. Addition of IL-12 to the medium increased th e lytic capacity of PBMC after CT only in the group with a good clinical re sponse (P < 0.05). Conclusions. NK cell numbers, CD8(+) T-cell levels, and CD8(+)/ CD28(+) cel l levels can be used as prognostic factors before CT. Our results suggest t hat 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 e xpression of IL-12 receptors or of an intracellular defect in the mechanism of transduction. These observations also provide support for human clinica l trials of IL-12 and neoadjuvant CT in patients with cervical cancer. (C) 2000 Academic Press.