NK Cell Activity in the Presence of IL-12 Is a Prognostic Assay to Neoadjuvant Chemotherapy in Cervical Cancer

Abstract

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/m2/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.