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Single-Molecule RNA Sequencing Reveals IFNγ-Induced Differential Expression of Immune Escape Genes in Merkel Cell Polyomavirus–Positive MCC Cell Lines

Merkel cell carcinoma (MCC) is a rare and highly aggressive cancer, which is mainly caused by genomic integration of the Merkel cell polyomavirus and subsequent expression of a truncated form of its large T antigen. The resulting primary tumor is known to be immunogenic and under constant pressure t...

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Autores principales: Sauerer, Tatjana, Lischer, Christopher, Weich, Adrian, Berking, Carola, Vera, Julio, Dörrie, Jan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727593/
https://www.ncbi.nlm.nih.gov/pubmed/35003017
http://dx.doi.org/10.3389/fmicb.2021.785662
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author Sauerer, Tatjana
Lischer, Christopher
Weich, Adrian
Berking, Carola
Vera, Julio
Dörrie, Jan
author_facet Sauerer, Tatjana
Lischer, Christopher
Weich, Adrian
Berking, Carola
Vera, Julio
Dörrie, Jan
author_sort Sauerer, Tatjana
collection PubMed
description Merkel cell carcinoma (MCC) is a rare and highly aggressive cancer, which is mainly caused by genomic integration of the Merkel cell polyomavirus and subsequent expression of a truncated form of its large T antigen. The resulting primary tumor is known to be immunogenic and under constant pressure to escape immune surveillance. Because interferon gamma (IFNγ), a key player of immune response, is secreted by many immune effector cells and has been shown to exert both anti-tumoral and pro-tumoral effects, we studied the transcriptomic response of MCC cells to IFNγ. In particular, immune modulatory effects that may help the tumor evade immune surveillance were of high interest to our investigation. The effect of IFNγ treatment on the transcriptomic program of three MCC cell lines (WaGa, MKL-1, and MKL-2) was analyzed using single-molecule sequencing via the Oxford Nanopore platform. A significant differential expression of several genes was detected across all three cell lines. Subsequent pathway analysis and manual annotation showed a clear upregulation of genes involved in the immune escape of tumor due to IFNγ treatment. The analysis of selected genes on protein level underlined our sequencing results. These findings contribute to a better understanding of immune escape of MCC and may help in clinical treatment of MCC patients. Furthermore, we demonstrate that single-molecule sequencing can be used to assess characteristics of large eukaryotic transcriptomes and thus contribute to a broader access to sequencing data in the community due to its low cost of entry.
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spelling pubmed-87275932022-01-06 Single-Molecule RNA Sequencing Reveals IFNγ-Induced Differential Expression of Immune Escape Genes in Merkel Cell Polyomavirus–Positive MCC Cell Lines Sauerer, Tatjana Lischer, Christopher Weich, Adrian Berking, Carola Vera, Julio Dörrie, Jan Front Microbiol Microbiology Merkel cell carcinoma (MCC) is a rare and highly aggressive cancer, which is mainly caused by genomic integration of the Merkel cell polyomavirus and subsequent expression of a truncated form of its large T antigen. The resulting primary tumor is known to be immunogenic and under constant pressure to escape immune surveillance. Because interferon gamma (IFNγ), a key player of immune response, is secreted by many immune effector cells and has been shown to exert both anti-tumoral and pro-tumoral effects, we studied the transcriptomic response of MCC cells to IFNγ. In particular, immune modulatory effects that may help the tumor evade immune surveillance were of high interest to our investigation. The effect of IFNγ treatment on the transcriptomic program of three MCC cell lines (WaGa, MKL-1, and MKL-2) was analyzed using single-molecule sequencing via the Oxford Nanopore platform. A significant differential expression of several genes was detected across all three cell lines. Subsequent pathway analysis and manual annotation showed a clear upregulation of genes involved in the immune escape of tumor due to IFNγ treatment. The analysis of selected genes on protein level underlined our sequencing results. These findings contribute to a better understanding of immune escape of MCC and may help in clinical treatment of MCC patients. Furthermore, we demonstrate that single-molecule sequencing can be used to assess characteristics of large eukaryotic transcriptomes and thus contribute to a broader access to sequencing data in the community due to its low cost of entry. Frontiers Media S.A. 2021-12-22 /pmc/articles/PMC8727593/ /pubmed/35003017 http://dx.doi.org/10.3389/fmicb.2021.785662 Text en Copyright © 2021 Sauerer, Lischer, Weich, Berking, Vera and Dörrie. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Sauerer, Tatjana
Lischer, Christopher
Weich, Adrian
Berking, Carola
Vera, Julio
Dörrie, Jan
Single-Molecule RNA Sequencing Reveals IFNγ-Induced Differential Expression of Immune Escape Genes in Merkel Cell Polyomavirus–Positive MCC Cell Lines
title Single-Molecule RNA Sequencing Reveals IFNγ-Induced Differential Expression of Immune Escape Genes in Merkel Cell Polyomavirus–Positive MCC Cell Lines
title_full Single-Molecule RNA Sequencing Reveals IFNγ-Induced Differential Expression of Immune Escape Genes in Merkel Cell Polyomavirus–Positive MCC Cell Lines
title_fullStr Single-Molecule RNA Sequencing Reveals IFNγ-Induced Differential Expression of Immune Escape Genes in Merkel Cell Polyomavirus–Positive MCC Cell Lines
title_full_unstemmed Single-Molecule RNA Sequencing Reveals IFNγ-Induced Differential Expression of Immune Escape Genes in Merkel Cell Polyomavirus–Positive MCC Cell Lines
title_short Single-Molecule RNA Sequencing Reveals IFNγ-Induced Differential Expression of Immune Escape Genes in Merkel Cell Polyomavirus–Positive MCC Cell Lines
title_sort single-molecule rna sequencing reveals ifnγ-induced differential expression of immune escape genes in merkel cell polyomavirus–positive mcc cell lines
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8727593/
https://www.ncbi.nlm.nih.gov/pubmed/35003017
http://dx.doi.org/10.3389/fmicb.2021.785662
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