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.


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.
Cosiski Marana
H R
HR
Department of Obstetrics and Gynecology, University of São Paulo, Ribeirão Preto, SP, 14049-900, Brazil.
Santana da Silva
J
J
Moreira de Andrade
J
J
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects / Q000276:immunology; D018664:Interleukin-12 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D018655:Lymphocyte Count / Q000187:drug effects; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D011379:Prognosis; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology
D000276:Adjuvants, Immunologic; D001761:Bleomycin; D018664:Interleukin-12; D002945:Cisplatin