Inherent transcriptional signatures of NK cells are associated with response to IFNΑ+rivabirin therapy in patients with Hepatitis C Virus

Maria Libera Ascierto, Federica Bozzano, Davide Bedognetti, Francesco Marras, Cathy Schechterly, Kentaro Matsuura, Antonino Picciotto, Simona Marenco, Yingdong Zhao, Valeria DeGiorgi, Michele Sommariva, Lorenzo Moretta, Ena Wang, Harvey J. Alter, Francesco M. Marincola, Andrea De Maria

Research output: Contribution to journalArticle

4 Citations (Scopus)

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 languageEnglish
Article number77
JournalJournal of Translational Medicine
Volume13
Issue number1
DOIs
Publication statusPublished - 1 Mar 2015

Fingerprint

Viruses
Natural Killer Cells
Hepacivirus
Polyethylene glycols
Natural Killer Cell Receptors
Transcription
Gene expression
Tumors
Modulation
RNA
Molecules
Therapeutics
Processing
Ubiquitination
Virus Diseases
Infection
Transcriptome
Genotype
Neoplasms

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 journalArticle

Ascierto, ML, Bozzano, F, Bedognetti, D, Marras, F, Schechterly, C, Matsuura, K, Picciotto, A, Marenco, S, Zhao, Y, DeGiorgi, V, Sommariva, M, Moretta, L, Wang, E, Alter, HJ, Marincola, FM & De Maria, A 2015, 'Inherent transcriptional signatures of NK cells are associated with response to IFNΑ+rivabirin therapy in patients with Hepatitis C Virus', Journal of Translational Medicine, vol. 13, no. 1, 77. https://doi.org/10.1186/s12967-015-0428-x
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. / Inherent transcriptional signatures of NK cells are associated with response to IFNΑ+rivabirin therapy in patients with Hepatitis C Virus. In: Journal of Translational Medicine. 2015 ; Vol. 13, No. 1.
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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.",
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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

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KW - Regulation of NK cells

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