Apoptotic Body-Loaded Dendritic Cells Efficiently Cross-Prime Cytotoxic T Lymphocytes Specific for NA17-A Antigen but Not for Melan-A/MART-1 Antigen
Résumé
DCs hold promise for cancer immunotherapy due to their functional ambivalence: iDCs internalize antigens, then mDCs trigger naive T-cell activation. However, no consensus has been reached concerning the optimal mode of antigen acquisition for efficient cross-priming of TAA-specific CTLs, and this remains a field of investigation. Here, we used highly purified apobodies derived from an HLA-A*0201-negative melanoma line as a source of tumor antigens for HLA-A*0201 DCs. We compared in vitro mDCs loaded with apobodies to DCs loaded with antigenic peptides, NA17-A 1-9 and Melan-A/MART-1 26-35 A27L analogue, for their capacity to stimulate melanoma antigen-specific T cells from autologous PBLs. Apobody phagocytosis did not induce spontaneous DC maturation, but phagocytic DCs were still responsive to mat-uration signals, resulting in a functional ability to activate antigen-specific lymphocytes. NA17-A-specific T lympho-cytes were activated by both types of stimulation, whereas only peptide-pulsed DCs stimulated the growth of Melan-A/ MART-1-specific lymphocytes. We also observed a lack of staining of melanoma-derived apobodies with a Melan-A-specific MAb, suggesting protein alteration during apoptosis induction. After HLA-A*0201/NA17-A multimer sorting, an-tigen-specific lymphocytes induced by mature DCs loaded with either peptide or apobodies displayed similar functional capacity against peptide-pulsed T2 cells and melanoma cells. Therefore, apobody-loaded DCs can achieve T-cell priming similar to that induced by peptide-pulsed DCs, provided that the apoptotic process allows the preservation of antigen expression .
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