Increase of human papillomavirus-16 E7-specific T helper type 1 response in peripheral blood of cervical cancer patients after radiotherapy

摘要

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: E751–70, E765–84 and E779–98. The cells were stained for CD4, CD69, intracellular interferon-γ (IFN-γ) and interleukin-4 (IL-4) cytokines and analysed by flow cytometry. A specific CD4⁺ CD69⁺ IFN-γ⁺ immune response against HPV-16 E779–98 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 E779–98-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-γ response in cervical cancer patients, rather than reflecting the host’s capability of controlling tumour growth, might be an indicator for disease severity.