Journal Article (Review Article)

DKFZ-2025-01683

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png IFN γ and the IFN γ Signaling Pathways in Merkel Cell Carcinoma.

Song, L. ; Guan, J. ; Zhou, Q. ; Liu, W. ; Becker, J.DKFZ* ; Deng, D.

2025
MDPI Basel

Abstract: Recent preclinical and clinical studies have confirmed the essential role of interferons in the host's immune response against malignant cells. Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer strongly associated with Merkel cell polyomavirus (MCPyV). Despite progress in understanding MCC pathogenesis, the role of innate immune signaling, particularly interferon-γ (IFN γ) and its downstream pathways, remains underexplored. This review summarizes recent findings on IFN-γ in MCC, highlighting its dual role in promoting both antitumor immunity and immune evasion. IFN-γ enhances cytotoxic T cell responses, upregulates MHC class I/II expression, and induces tumor cell apoptosis. Transcriptomic studies have shown that IFN-γ treatment upregulates immune-regulatory genes including PD-L1, HLA-A/B/C, and IDO1 by over threefold; it also activates APOBEC3B and 3G, contributing to antiviral defense and tumor editing. Clinically, immune checkpoint inhibitors (ICIs) such as pembrolizumab and avelumab yield objective response rates of 30-56% and two-year overall survival rates exceeding 60% in advanced MCC. However, approximately 50% of patients do not respond, in part due to IFN-γ signaling deficiencies. This review further discusses IFN-γ's crosstalk with the STAT1/3/5 pathways and emerging combination strategies aimed at restoring immune sensitivity. Understanding these mechanisms may inform personalized immunotherapeutic approaches and guide the development of IFN-γ-based interventions in MCC.

Keyword(s): Merkel cell carcinoma ; immune evasion ; immunotherapy ; interferon-gamma (IFN γ) ; tumor microenvironment

Note: Becker? / German Cancer Consortium (DKTK), Deutsches Krebsforschung Institut, 69120 Heidelberg, Germany

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Essen/Düsseldorf (ED01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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