title: Apoptotic body-loaded dendritic cells efficiently cross-prime cytotoxic T lymphocytes specific for NA17-A antigen but not for Melan-A/MART-1 antigen.
abstract: 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 maturation signals, resulting in a functional ability to activate antigen-specific lymphocytes. NA17-A-specific T lymphocytes 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, antigen-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.
authors.affiliation: INSERM U463, Nantes, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Labarrière
authors.forename: Laurent
authors.initials: L
authors.lastname: Bretaudeau
authors.forename: Nadine
authors.initials: N
authors.lastname: Gervois
authors.forename: Marie
authors.initials: M
authors.lastname: Bodinier
authors.forename: Gwenola
authors.initials: G
authors.lastname: Bougras
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Diez
authors.forename: François
authors.initials: F
authors.lastname: Lang
authors.forename: Marc
authors.initials: M
authors.lastname: Gregoire
authors.forename: Francine
authors.initials: F
authors.lastname: Jotereau
mesh_terms: D017951:Antigen Presentation / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D006801:Humans; D018189:Immunomagnetic Separation; D058965:MART-1 Antigen; D009363:Neoplasm Proteins / Q000276:immunology*; D010446:Peptide Fragments / Q000276:immunology*; D010587:Phagocytosis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
chemical_list: D000951:Antigens, Neoplasm; D058965:MART-1 Antigen; C548667:MLANA protein, human; D009363:Neoplasm Proteins; D010446:Peptide Fragments