HPV16-specific cytotoxic T lymphocyte responses are detected in all HPV16-positive cervical cancer patients.
OBJECTIVE
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 immunotherapeutic strategies. The aim of the study was to investigate the HPV16 E6/E7-specific CTL immune response in a group of untreated HPV16-positive cervical cancer patients.


METHODS
Peripheral blood mononuclear cells from 21 untreated cervical cancer patients and 4 healthy controls were isolated prior to any therapy. Autologous monocyte-derived dendritic cells (MDDCs) were transiently transfected with HPV16 E6 or E7 expression vectors and used for one round of in vitro restimulation and as target cells in chromium release assays with restimulated peripheral blood lymphocytes.


RESULTS
Transfected monocyte-derived dendritic cells were differentiated to exhibit a fully mature phenotype. HPV16 E6 and E7 transgenes were expressed and translated as measured by RT-PCR and intracellular flow cytometry, respectively. All HPV16-associated cervical cancer patients showed evidence of specific CTLs. Lytic activity for HPV16 E6 (11/12) and/or E7 (8/9) was above 30% at the 100:1 effector to target ratio. None of the HPV16-negative cervical cancer patients or healthy controls were above 15% of lysis.


CONCLUSIONS
These data suggest that HPV-specific cytolytic immune responses can be detected in all untreated cervical cancer patients. Our approach, using dendritic cells for restimulation and as target cells, may enhance immunomonitoring of cervical cancer patients.
Valdespino
Victor
V
Laboratory of Genomic Medicine, UNISSER, Faculty of Medicine, Universidad Nacional Autónoma de México/Servicio de Genética y Medicina Genómica, Hospital General de México, Mexico City, México.
Gorodezky
Clara
C
Ortiz
Vianney
V
Kaufmann
Andreas M
AM
Roman-Basaure
Edgar
E
Vazquez
Alejandra
A
Berumen
Jaime
J
D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000502:physiology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D006801:Humans; D009856:Oncogene Proteins, Viral / Q000235:genetics / Q000276:immunology*; D050725:Papillomavirus E7 Proteins; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology*; D010957:Plasmids / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000821:virology*
C068651:E6 protein, Human papillomavirus type 16; D018984:Epitopes, T-Lymphocyte; D009856:Oncogene Proteins, Viral; D050725:Papillomavirus E7 Proteins; D012097:Repressor Proteins; C059731:oncogene protein E7, Human papillomavirus type 16