期刊
CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 64, 期 11, 页码 1419-1427出版社
SPRINGER
DOI: 10.1007/s00262-015-1741-1
关键词
Monocyte-derived dendritic cell; IL-4; IFN alpha; Antigen presentation; Vaccination
资金
- Cancer Center Amsterdam/VUmc Institute for Cancer [CCA 2007-5-09]
Dendritic cells (DC) vaccination is a potent therapeutic approach for inducing tumor-directed immunity, but challenges remain. One of the particular interest is the induction of an immune response targeting multiple (unknown) tumor-associated antigens (TAA), which requires a polyvalent source of TAA. Previously, we described the preferred use of apoptotic cell-derived blebs over the larger apoptotic cell remnants, as a source of TAA for both in situ loading of skin-resident DC and in vitro loading of monocyte-derived DC (MoDC). Recent reports suggest that MoDC cultured in the presence of GM-CSF supplemented with IFN alpha (IFN alpha MoDC), as compared to IL-4 (IL-4 MoDC), have an increased capacity to cross-present antigen to CD8(+) T cells. As culture conditions, maturation methods and antigen sources differ between the conducted studies, we analyzed the functional differences between IL-4 MoDC and IFN alpha MoDC, loaded with blebs, in a head-to-head comparison using commonly used protocols. Our data show that both MoDC types are potent (cross-) primers of CD8(+) T cells. Whereas IFN alpha MoDC were more potent in their capacity to cross-present a 25-mer MART-1 synthetic long peptide (SLP) to a MART-1(aa26-35) recognizing CD8(+) T cell line, IL-4 MoDC proved more potent cross-primers of antigen-specific CD8(+) T cells when loaded with blebs. The latter is likely due to the observed greater capacity of IL-4 MoDC to ingest apoptotic blebs. In conclusion, our data indicate the use of IFN alpha MoDC over IL-4 MoDC in the context of DC vaccination with SLP, whereas IL-4 MoDC are preferred for vaccination with bleb-derived antigens.
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