Combined cytotoxic activity of an infectious, but non-replicative herpes simplex virus type 1 and plasmacytoid dendritic cells against tumour cells
Thomann S, Boscheinen J, Vogel K, Knipe DM, Deluca N, Gross S, Schuler-Thurner B, Schuster P, Schmidt B (2015)
Publication Type: Journal article
Publication year: 2015
Journal
Book Volume: 146
Pages Range: 327-38
Journal Issue: 2
DOI: 10.1111/imm.12509
Abstract
Malignant melanoma is an aggressive tumour of the skin with increasing incidence, frequent metastasis and poor prognosis. At the same time, it is an immunogenic type of cancer with spontaneous regressions. Most recently, the tumoricidal effect of plasmacytoid dendritic cells (pDC) and their capacity to overcome the immunosuppressive tumour microenvironment are being investigated. In this respect, we studied the effect of the infectious, but replication-deficient, herpes simplex virus 1 (HSV-1) d106S vaccine strain, which lacks essential immediate early genes, in pDC co-cultures with 11 melanoma cell lines. We observed a strong cytotoxic activity, inducing apoptotic and necrotic cell death in most melanoma cell lines. The cytotoxic activity of HSV-1 d106S plus pDC was comparable to the levels of cytotoxicity induced by natural killer cells, but required only a fraction of cells with effector : target ratios of 1 : 20 (P < 0·05). The suppressive activity of cell-free supernatants derived from virus-stimulated pDC was significantly neutralized using antibodies against the interferon-? receptor (P < 0·05). In addition to type I interferons, TRAIL and granzyme B contributed to the inhibitory effect of HSV-1 d106S plus pDC to a minor extent. UV-irradiated viral stocks were significantly less active than infectious particles, both in the absence and presence of pDC (P < 0·05), indicating that residual activity of HSV-1 d106S is a major component and sensitizes the tumour cells to interferon-producing pDC. Three leukaemic cell lines were also susceptible to this treatment, suggesting a general anti-tumour effect. In conclusion, the potential of HSV-1 d106S for therapeutic vaccination should be further evaluated in patients suffering from different malignancies.
Authors with CRIS profile
Sabrina Thomann
Department of Molecular Immunology
Jan Boscheinen
Professur für Virologie
Beatrice Schuler-Thurner
Lehrstuhl für Haut- und Geschlechtskrankheiten
Involved external institutions
Universität Regensburg
Germany (DE)
University of Pittsburgh
United States (USA) (US)
Harvard University
United States (USA) (US)
Germany (DE)
University of Pittsburgh
United States (USA) (US)
Harvard University
United States (USA) (US)
How to cite
APA:
Thomann, S., Boscheinen, J., Vogel, K., Knipe, D.M., Deluca, N., Gross, S.,... Schmidt, B. (2015). Combined cytotoxic activity of an infectious, but non-replicative herpes simplex virus type 1 and plasmacytoid dendritic cells against tumour cells. Immunology, 146(2), 327-38. https://doi.org/10.1111/imm.12509
MLA:
Thomann, Sabrina, et al. "Combined cytotoxic activity of an infectious, but non-replicative herpes simplex virus type 1 and plasmacytoid dendritic cells against tumour cells." Immunology 146.2 (2015): 327-38.
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