Type-1 polarized dendritic cells loaded with apoptotic prostate cancer cells are potent inducers of CD8(+) T cells against prostate cancer cells and defined prostate cancer-specific epitopes.

ABSTRACT: In order to develop improved vaccines for patients with recurrent prostate cancer (PCa), we tested the feasibility of using type-1 polarized dendritic cells (?DC1s) to cross-present antigens from allogeneic PCa cells and to induce functional CD8(+) T cell responses against PCa cells and against defined MHC class I-restricted PCa-relevant epitopes.Monocyte-derived DCs from PCa patients were matured using the "standard" cytokine cocktail (IL-1?/TNF?/IL-6/PGE?) or using the ?DC1-polarizing cocktail (IL-1?/TNF?/IFN?/IFN?/poly-I:C), loaded with UV-irradiated LNCaP cells, and used to sensitize autologous CD8(+) T cells.?DC1s from PCa patients secreted 10-30 times higher levels of IL-12p70 than sDCs. Importantly this elevated capacity for IL-12p70 secretion was not inhibited by loading with apoptotic tumor cells. Compared to standard DCs, ?DC1s induced higher numbers of CD8(+) T cells capable of recognizing both the original PCa cells as well as another PCa cell line, DU145, in MHC class I-restricted fashion. Furthermore, ?DC1s induced higher numbers of CD8(+) T cells recognizing defined PCa-specific class I-restricted peptide epitopes of prostate-specific antigen and prostatic acid phosphatase: PAP(135-143) (average 49-fold higher), PAP(112-120) (average 24-fold), PSA(141-150) (average 5.5-fold), and PSA(146-154) (average 11-fold).Type-1 polarization of GM-CSF/IL-4-generated DCs enhances their ability to present allogeneic tumor cells and to induce CD8(+) T cells recognizing different PCa cells and multiple defined PCa-specific epitopes. These observations help to develop improved immunotherapies of PCa for patients with different HLA types and lacking autologous tumor material.

SUBMITTER: Wieckowski E 

PROVIDER: S-EPMC2989344 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature