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000303492 1001_ $$aSong, Lina$$b0
000303492 245__ $$aIFN γ and the IFN γ Signaling Pathways in Merkel Cell Carcinoma.
000303492 260__ $$aBasel$$bMDPI$$c2025
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000303492 500__ $$aBecker? / German Cancer Consortium (DKTK), Deutsches Krebsforschung Institut, 69120 Heidelberg, Germany
000303492 520__ $$aRecent 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.
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000303492 650_7 $$2Other$$aMerkel cell carcinoma
000303492 650_7 $$2Other$$aimmune evasion
000303492 650_7 $$2Other$$aimmunotherapy
000303492 650_7 $$2Other$$ainterferon-gamma (IFN γ)
000303492 650_7 $$2Other$$atumor microenvironment
000303492 7001_ $$aGuan, Jinye$$b1
000303492 7001_ $$aZhou, Qunmei$$b2
000303492 7001_ $$aLiu, Wenshang$$b3
000303492 7001_ $$0P:(DE-He78)7bf2f090fe39a6cd6f0bccf5ea2d4fb3$$aBecker, Jürgen$$b4$$udkfz
000303492 7001_ $$00000-0001-7317-283X$$aDeng, Dan$$b5
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