Abstract
Background: Differences in the expression of Natural Killer cell receptors have been reported to reflect divergent clinical courses in patients with chronic infections or tumors. However, extensive molecular characterization at the transcriptional level to support this view is lacking. The aim of this work was to characterize baseline differences in purified NK cell transcriptional activity stratified by response to treatment with PEG-IFNΑ/RBV in patients chronically infected with HCV. Methods: To this end we here studied by flow cytometer and gene expression profile, phenotypic and transcriptional characteristics of purified NK cells in patients chronically infected with HCV genotype-1 virus who were subsequently treated with PEG-IFNΑ/RBV. Results were further correlated with divergent clinical response obtained after treatment. Results: The pre-treatment transcriptional patterns of purified NK cells from patients subsequently undergoing a sustained virologic response (SVR) clearly segregated from those of non-responder (NR) patients. A set of 476 transcripts, including molecules involved in RNA processing, ubiquitination pathways as well as HLA class II signalling were differently expressed among divergent patients. In addition, treatment outcome was associated with differences in surface expression of NKp30 and NKG2D. A complex relationship was observed that suggested for extensive post-transcriptional editing. Only a small number of the NK cell transcripts identified were correlated with chronic HCV infection/replication indicating that inherent transcriptional activity prevails over environment effects such as viral infection. Conclusions: Collectively, inherent/genetic modulation of NK cell transcription is involved in setting the path to divergent treatment outcomes and could become useful to therapeutic advantage.
| Original language | English |
|---|---|
| Article number | 77 |
| Journal | Journal of Translational Medicine |
| Volume | 13 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 1 Mar 2015 |
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Keywords
- Clinical response
- HCV infection
- NK cells
- Regulation of NK cells
ASJC Scopus subject areas
- Medicine(all)
- Biochemistry, Genetics and Molecular Biology(all)
Cite this
Inherent transcriptional signatures of NK cells are associated with response to IFNΑ+rivabirin therapy in patients with Hepatitis C Virus. / Ascierto, Maria Libera; Bozzano, Federica; Bedognetti, Davide; Marras, Francesco; Schechterly, Cathy; Matsuura, Kentaro; Picciotto, Antonino; Marenco, Simona; Zhao, Yingdong; DeGiorgi, Valeria; Sommariva, Michele; Moretta, Lorenzo; Wang, Ena; Alter, Harvey J.; Marincola, Francesco M.; De Maria, Andrea.
In: Journal of Translational Medicine, Vol. 13, No. 1, 77, 01.03.2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Inherent transcriptional signatures of NK cells are associated with response to IFNΑ+rivabirin therapy in patients with Hepatitis C Virus
AU - Ascierto, Maria Libera
AU - Bozzano, Federica
AU - Bedognetti, Davide
AU - Marras, Francesco
AU - Schechterly, Cathy
AU - Matsuura, Kentaro
AU - Picciotto, Antonino
AU - Marenco, Simona
AU - Zhao, Yingdong
AU - DeGiorgi, Valeria
AU - Sommariva, Michele
AU - Moretta, Lorenzo
AU - Wang, Ena
AU - Alter, Harvey J.
AU - Marincola, Francesco M.
AU - De Maria, Andrea
PY - 2015/3/1
Y1 - 2015/3/1
N2 - Background: Differences in the expression of Natural Killer cell receptors have been reported to reflect divergent clinical courses in patients with chronic infections or tumors. However, extensive molecular characterization at the transcriptional level to support this view is lacking. The aim of this work was to characterize baseline differences in purified NK cell transcriptional activity stratified by response to treatment with PEG-IFNΑ/RBV in patients chronically infected with HCV. Methods: To this end we here studied by flow cytometer and gene expression profile, phenotypic and transcriptional characteristics of purified NK cells in patients chronically infected with HCV genotype-1 virus who were subsequently treated with PEG-IFNΑ/RBV. Results were further correlated with divergent clinical response obtained after treatment. Results: The pre-treatment transcriptional patterns of purified NK cells from patients subsequently undergoing a sustained virologic response (SVR) clearly segregated from those of non-responder (NR) patients. A set of 476 transcripts, including molecules involved in RNA processing, ubiquitination pathways as well as HLA class II signalling were differently expressed among divergent patients. In addition, treatment outcome was associated with differences in surface expression of NKp30 and NKG2D. A complex relationship was observed that suggested for extensive post-transcriptional editing. Only a small number of the NK cell transcripts identified were correlated with chronic HCV infection/replication indicating that inherent transcriptional activity prevails over environment effects such as viral infection. Conclusions: Collectively, inherent/genetic modulation of NK cell transcription is involved in setting the path to divergent treatment outcomes and could become useful to therapeutic advantage.
AB - Background: Differences in the expression of Natural Killer cell receptors have been reported to reflect divergent clinical courses in patients with chronic infections or tumors. However, extensive molecular characterization at the transcriptional level to support this view is lacking. The aim of this work was to characterize baseline differences in purified NK cell transcriptional activity stratified by response to treatment with PEG-IFNΑ/RBV in patients chronically infected with HCV. Methods: To this end we here studied by flow cytometer and gene expression profile, phenotypic and transcriptional characteristics of purified NK cells in patients chronically infected with HCV genotype-1 virus who were subsequently treated with PEG-IFNΑ/RBV. Results were further correlated with divergent clinical response obtained after treatment. Results: The pre-treatment transcriptional patterns of purified NK cells from patients subsequently undergoing a sustained virologic response (SVR) clearly segregated from those of non-responder (NR) patients. A set of 476 transcripts, including molecules involved in RNA processing, ubiquitination pathways as well as HLA class II signalling were differently expressed among divergent patients. In addition, treatment outcome was associated with differences in surface expression of NKp30 and NKG2D. A complex relationship was observed that suggested for extensive post-transcriptional editing. Only a small number of the NK cell transcripts identified were correlated with chronic HCV infection/replication indicating that inherent transcriptional activity prevails over environment effects such as viral infection. Conclusions: Collectively, inherent/genetic modulation of NK cell transcription is involved in setting the path to divergent treatment outcomes and could become useful to therapeutic advantage.
KW - Clinical response
KW - HCV infection
KW - NK cells
KW - Regulation of NK cells
UR - http://www.scopus.com/inward/record.url?scp=84924988190&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84924988190&partnerID=8YFLogxK
U2 - 10.1186/s12967-015-0428-x
DO - 10.1186/s12967-015-0428-x
M3 - Article
C2 - 25849716
AN - SCOPUS:84924988190
VL - 13
JO - Journal of Translational Medicine
JF - Journal of Translational Medicine
SN - 1479-5876
IS - 1
M1 - 77
ER -