title: Increase of human papillomavirus-16 E7-specific T helper type 1 response in peripheral blood of cervical cancer patients after radiotherapy.
abstract: It has been suggested that tumour cell lysis by gamma-radiation induces a tumoral antigen release eliciting an immune response. It is not clear how a specific immune response in cervical cancer patients is developed after radiotherapy. This study is an attempt to investigate the role of the human papillomavirus type 16 (HPV-16) E7-specific T helper response before and after radiotherapy. Lymphocytes were isolated from 32 cervical cancer patients before and after radiotherapy and from 16 healthy women. They were stimulated for 12 hr with autologous HPV-16 E7-pulsed monocyte-derived dendritic cells or directly with HPV-16 E7 synthetic peptides: E7(51-70), E7(65-84) and E7(79-98). The cells were stained for CD4, CD69, intracellular interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) cytokines and analysed by flow cytometry. A specific CD4(+) CD69(+) IFN-gamma(+) immune response against HPV-16 E7(79-98) peptide was observed in 10 of 14 patients (71.4%) after treatment, compared with 4 of 14 (28.5%) before radiotherapy (P = 0.039); however, this response was not associated with a successful clinical response. Before treatment, 5 of 31 patients showed a HPV-16 E7(79-98)-specific T helper type 2 (Th2) response. Interestingly, this response was significantly associated with a decrease in disease-free survival (P = 0.027). These results suggest that a Th2-type cellular response could be useful as a predictor of recurrence and poor prognosis. An increase of the HPV-specific immune response was observed after radiotherapy; however, it is not enough to control completely the disease after treatment. Our results support that the E7-specific T-cell IFN-gamma response in cervical cancer patients, rather than reflecting the host's capability of controlling tumour growth, might be an indicator for disease severity.
authors.affiliation: Grupo de Investigación en Biología del Cáncer, Instituto Nacional de Cancerología, Bogotá, Columbia.
authors.forename: Félix Giovanni
authors.initials: FG
authors.lastname: Delgado
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Martínez
authors.forename: María Angélica
authors.initials: MA
authors.lastname: Céspedes
authors.forename: María Mercedes
authors.initials: MM
authors.lastname: Bravo
authors.forename: María Cristina
authors.initials: MC
authors.lastname: Navas
authors.forename: Alba Lucía
authors.initials: AL
authors.lastname: Cómbita Rojas
mesh_terms: D003713:Dendritic Cells / Q000276:immunology; D005260:Female; D005500:Follow-Up Studies; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D052162:Human papillomavirus 16 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D050725:Papillomavirus E7 Proteins / Q000276:immunology* / Q000378:metabolism; D030361:Papillomavirus Infections / Q000150:complications / Q000276:immunology*; D016019:Survival Analysis; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000532:radiotherapy* / Q000821:virology
chemical_list: D015395:Histocompatibility Antigens Class I; D050725:Papillomavirus E7 Proteins; D015847:Interleukin-4; D007371:Interferon-gamma
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