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Controlled infection with a therapeutic virus defines the activation kinetics of human natural killer cells in vivo
- Source :
- Clinical and Experimental Immunology. 180:98-107
- Publication Year :
- 2015
- Publisher :
- Oxford University Press (OUP), 2015.
-
Abstract
- Summary Human natural killer (NK) cells play an important role in anti-viral immunity. However, studying their activation kinetics during infection is highly problematic. A clinical trial of a therapeutic virus provided an opportunity to study human NK cell activation in vivo in a controlled manner. Ten colorectal cancer patients with liver metastases received between one and five doses of oncolytic reovirus prior to surgical resection of their tumour. NK cell surface expression of the interferon-inducible molecules CD69 and tetherin peaked 24–48 h post-infection, coincident with a peak of interferon-induced gene expression. The interferon response and NK cell activation were transient, declining by 96 h post-infection. Furthermore, neither NK cell activation nor the interferon response were sustained in patients undergoing multiple rounds of virus treatment. These results show that reovirus modulates human NK cell activity in vivo and suggest that this may contribute to any therapeutic effect of this oncolytic virus. Detection of a single, transient peak of activation, despite multiple treatment rounds, has implications for the design of reovirus-based therapy. Furthermore, our results suggest the existence of a post-infection refractory period when the interferon response and NK cell activation are blunted. This refractory period has been observed previously in animal models and may underlie the enhanced susceptibility to secondary infections that is seen following viral infection.
- Subjects :
- Antigens, Differentiation, T-Lymphocyte
Male
Secondary infection
Immunology
Cell
Biology
Reoviridae
Virus
Antigens, CD
Interferon
In vivo
Neoplasms
medicine
Humans
Immunology and Allergy
Lectins, C-Type
Aged
Oncolytic Virotherapy
Immunity, Cellular
Lymphokine-activated killer cell
Original Articles
Middle Aged
Oncolytic virus
Killer Cells, Natural
Oncolytic Viruses
medicine.anatomical_structure
Tetherin
Female
Interferons
medicine.drug
Subjects
Details
- ISSN :
- 13652249 and 00099104
- Volume :
- 180
- Database :
- OpenAIRE
- Journal :
- Clinical and Experimental Immunology
- Accession number :
- edsair.doi.dedup.....d1973fb795c67ad6c4fdddacddd30ced
- Full Text :
- https://doi.org/10.1111/cei.12562