The specific CTL response against human papillomavirus (HPV) antigens in women with cervical cancer has been poorly studied. Immunological monitoring of this response is central for understanding the principles that underlie successful im munotherapeutic strategies. The aim of the study was to investigate the HPV16 E6 /E7-specific CTL immune response in a group of untreated HPV16-positive cervic al cancer patients. Peripheral blood mononuclear cells from 21 untreated cervica l cancer patients and 4 healthy controls were isolated prior to any therapy. Aut ologous monocyte-derived dendritic cells (MDDCs) were transiently transfected w ith HPV16 E6 or E7 expression vectors and used for one round of in vitro restimu lation and as target cells in chromium release assays with restimulated peripher al blood lymphocytes. Transfected monocyte-derived dendritic cells were differe ntiated to exhibit a fully mature phenotype. HPV16 E6and E7 transgenes were expr essed and translated as measured by RT-PCR and intracellular flow cytometry, re spectively. All HPV16-associated cervical cancer patients showed evidence of sp ecific CTLs. Lytic activity for HPV16 E6 (11/12) and/or E7 (8/9) was above 30%a t the 100:1 effector to target ratio. None of the HPV16-negative cervical cance r patients or healthy controls were above 15%of lysis. These data suggest that HPV-specific cytolytic immune responses can be detected in all untreated cervic al cancer patients. Our approach, using dendritic cells for restimulation and as target cells, may enhance immunomonitoring of cervical cancer patients.
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