Abstract
The major type I interferon-producing plasmacytoid dendritic cells (pDC) surround and infiltrate certain tumors like malignant melanoma, head and neck cancer, and ovarian and breast cancer. The presence of pDC in these tumors is associated with an unfavorable prognosis for the patients as long as these cells are unstimulated. Upon activation by synthetic Toll-like receptor agonists or viruses, however, pDC develop cytotoxic activities. Viruses have the additional advantage to augment cytotoxic activities of pDC via lytic replication in malignant lesions. These effects turn cold tumors into hotspots, recruiting further immune cells to the site of inflammation. Activated pDC contribute to cross-presentation of tumor-associated antigens by classical dendritic cells, which induce cytotoxic T-cells in particular in the presence of checkpoint inhibitors. The modification of oncolytic herpes viruses via genetic engineering favorably affects this process through the enhanced production of pro-inflammatory cytokines, curbing of tumor blood supply, and removal of extracellular barriers for efficient viral spread. Importantly, viral vectors may contribute to stimulation of memory-type adaptive immune responses through presentation of tumor-related neo- and/or self-antigens. Eventually, both replication-competent and replication-deficient herpes simplex virus 1 (HSV-1) may serve as vaccine vectors, which contribute to tumor regression by the stimulation of pDC and other dendritic cells in adjuvant and neo-adjuvant situations.
Highlights
Based on early observations of lineage-negative cells with dendritic cell (DC)-like morphology [1,2], plasmacytoid dendritic cells were characterized by two independent groups in 1999 as the main type I interferon (IFN)-producing cells in the blood upon stimulation with herpes simplex or influenza viruses [3,4]
Stimulation of plasmacytoid dendritic cells (pDC) with herpes simplex virus 1 (HSV-1) prior to co-culture significantly reduced the cytotoxic activity, which demonstrated that the infection of melanoma cell cultures by herpes virus (HSV)-1 contributed to the oncolytic effect of pDC
Oncolytic herpes viruses provide a unique opportunity to treat and to vaccinate against certain tumors. These effects are amplified by pDC, which surround and infiltrate certain types of cancer
Summary
Based on early observations of lineage-negative cells with dendritic cell (DC)-like morphology [1,2], plasmacytoid dendritic cells (pDC) were characterized by two independent groups in 1999 as the main type I interferon (IFN)-producing cells in the blood upon stimulation with herpes simplex or influenza viruses [3,4]. Recent evidence suggests that pDC are a heterogeneous cell population consisting of a majority of “conventional” pDC and a minority of “pDC-like cells” originating from common lymphoid and common dendritic cell (DC) precursors, respectively [5]. The purpose of our review is not to repeat these findings but to focus on the role of pDC in anti-tumor defenses in the context of oncolytic herpes simplex virus 1 (HSV-1).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
