Abstract
BackgroundCervical cancer is the second most common gynecological cancer amongst women world-wide. Despite optimized protocols, standard treatments still face several disadvantages. Therefore, research aims at the development of immune-based strategies using tumor antigen-loaded dendritic cells for the induction of cellular anti-tumor immunity.ResultsIn this study, we used dendritic cells loaded with the HLA-A2-restricted HPV type 16 E711–20 peptide in order to induce an in vitro CD8+ T cell response. For this purpose, peptide-pulsed dendritic cells were co-cultured with autologous CD8+ T cells. After 5 weekly stimulations with peptide-pulsed mature dendritic cells, cultured T cells were analyzed for antigen specificity by an IFN-γ ELISPOT assay. Using this ELISPOT assay, we were able to detect E7-specific IFN-γ-secreting CD8+ T cells in 5/5 healthy donors.ConclusionWe show that peptide-pulsed mature dendritic cells are able to stimulate a HPV type 16 E7 peptide-specific immune response in vitro. These experiments describe an efficient culture protocol for antigen-specific T cells for use in pre-clinical vaccination research and confirm the need for sensitive T cell assays for detection of tumor-specific immune responses in vitro.
Highlights
Cervical cancer is the second most common gynecological cancer amongst women world-wide
Peptide-pulsed dendritic cells (DC) efficiently present a major histocompatibility complex (MHC) class Irestricted E7 peptide to CD8+ T cells First, we evaluated if our cultured mature DC population was able to present the YMLDLQPETT peptide to CD8+ T cells in a MHC class I-dependent way
We showed that peptide-pulsed mature DC are able to induce a cellular response against human papillomavirus (HPV)-16 in 5/5 healthy volunteers, as detected by E7-specific IFN-γ producing CD8+ T cells in an enzyme-linked immunospot (ELISPOT) analysis
Summary
Cervical cancer is the second most common gynecological cancer amongst women world-wide. Cervical cancer contributes to approximately 12% of the global cancer burden in women and represents the second most frequent gynecological malignancy in the world [1,2]. An additional disadvantage of radio- and chemotherapy is a pronounced and long-lasting negative effect on the immune system. For these reasons, current research aims at the development of new and more efficient strategies. Current research aims at the development of new and more efficient strategies In this context, dendritic cells (DC) loaded with tumor antigens for activation and/or expansion of tumor-specific T cells are cur-
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