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Clin Cancer Res. 2013 Mar 1;19(5):1147-58. doi: 10.1158/1078-0432.CCR-12-2733. Epub 2013 Jan 21.

Measles virus vaccine-infected tumor cells induce tumor antigen cross-presentation by human plasmacytoid dendritic cells.

Author information

1
Institut National de la Santé et de la Recherche Medicale, UMR892, Centre National de la Recherche Scientifique, UMR6299, Université de Nantes, Nantes, France.

Abstract

PURPOSE:

Plasmacytoid dendritic cells (pDC) are antigen-presenting cells specialized in antiviral response. The measles virus vaccine is proposed as an antitumor agent to target and specifically kill tumor cells without infecting healthy cells.

EXPERIMENTAL DESIGN:

Here, we investigated, in vitro, the effects of measles virus vaccine-infected tumor cells on the phenotype and functions of human pDC. We studied maturation and tumor antigen cross-presentation by pDC, exposed either to the virus alone, or to measles virus vaccine-infected or UV-irradiated tumor cells.

RESULTS:

We found that only measles virus vaccine-infected cells induced pDC maturation with a strong production of IFN-α, whereas UV-irradiated tumor cells were unable to activate pDC. This IFN-α production was triggered by the interaction of measles virus vaccine single-stranded RNA (ssRNA) with TLR7. We observed that measles virus vaccine-infected tumor cells were phagocytosed by pDC. Interestingly, we showed cross-presentation of the tumor antigen NYESO-1 to a specific CD8(+) T-cell clone when pDC were cocultured with measles virus vaccine-infected tumor cells, whereas pDC were unable to cross-present NYESO-1 after coculture with UV-irradiated tumor cells.

CONCLUSIONS:

Altogether, our results suggest that the use of measles virus vaccine in antitumor virotherapy induces immunogenic tumor cell death, allowing pDC to mature, produce high amounts of IFN-α, and cross-present tumor antigen, thus representing a mode of recruiting these antigen-presenting cells in the immune response. Clin Cancer Res; 19(5); 1147-58. ©2012 AACR.

PMID:
23339127
DOI:
10.1158/1078-0432.CCR-12-2733
[Indexed for MEDLINE]
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