Buchumschlag

STAT1 and STAT3 exhibit a crosstalk and are associated with increased inflammation in hepatocellular carcinoma

Liver cancers, which are mostly hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are very aggressive tumors with poor prognosis. Therapeutic options with curative intent are largely limited to surgery and available systemic therapies show limited benefit. Signal transducer and activator...

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Hauptverfasser: Plöger, Carolin (VerfasserIn) , Schreck, Johannes (VerfasserIn) , Huth, Thorben (VerfasserIn) , Fraas, Angelika (VerfasserIn) , Albrecht, Thomas (VerfasserIn) , Charbel, Alphonse (VerfasserIn) , Ji, Junfang (VerfasserIn) , Singer, Stephan (VerfasserIn) , Breuhahn, Kai (VerfasserIn) , Pusch, Stefan (VerfasserIn) , Köhler, Bruno Christian (VerfasserIn) , Springfeld, Christoph (VerfasserIn) , Schirmacher, Peter (VerfasserIn) , Mehrabi, Arianeb (VerfasserIn) , Goeppert, Benjamin (VerfasserIn) , Rössler, Stephanie (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 23 February 2022
In: Cancers
Year: 2022, Jahrgang: 14, Heft: 5
ISSN:2072-6694
DOI:10.3390/cancers14051154
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cancers14051154
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2072-6694/14/5/1154
Volltext
Verfasserangaben:Carolin Ploeger, Johannes Schreck, Thorben Huth, Angelika Fraas, Thomas Albrecht, Alphonse Charbel, Junfang Ji, Stephan Singer, Kai Breuhahn, Stefan Pusch, Bruno Christian Köhler, Christoph Springfeld, Peter Schirmacher, Arianeb Mehrabi, Benjamin Goeppert and Stephanie Roessler
Beschreibung
Zusammenfassung:Liver cancers, which are mostly hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), are very aggressive tumors with poor prognosis. Therapeutic options with curative intent are largely limited to surgery and available systemic therapies show limited benefit. Signal transducer and activator of transcription 1 (STAT1) and 3 (STAT3) are key transcription factors activated by pro-inflammatory cytokines such as interferon-γ (IFN-γ) and interleukin-6 (IL-6). In this study, we combined in vitro cell culture experiments and immunohistochemical analyses of human HCC (N = 124) and CCA (N = 138) specimens. We observed that in the absence of STAT3, IL-6 induced the activation of STAT1 and its target genes suggesting that IL-6 derived from the tumor microenvironment may activate both STAT1 and STAT3 target genes in HCC tumor cells. In addition, STAT1 and STAT3 were highly activated in a subset of HCC, which exhibited a high degree of infiltrating CD8- and FOXP3-positive immune cells and PD-L1 expression. Our results demonstrate that STAT1 and STAT3 are expressed and activated in HCC and tumor infiltrating immune cells. In addition, HCC cases with high STAT1 and STAT3 expression also exhibited a high degree of immune cell infiltration, suggesting increased immunological tolerance.
Beschreibung:Published: 23 February 2022
Gesehen am 27.09.2022
Beschreibung:Online Resource
ISSN:2072-6694
DOI:10.3390/cancers14051154

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