RECQL4 affects MHC class II-mediated signalling and favours an immune-evasive signature that limits response to immune checkpoint inhibitor therapy in patients with malignant melanoma

Sara Egea-Rodriguez; Renáta Váraljai; Thierry M. Nordmann; Restuan Lubis; Manuel Philip; Florian Rambow; Alexander Roesch; Michael Flaig; Susanne Horn; Raphael Stoll; Fang Zhao; Annette Paschen; Bert Klebl; Ian D. Hickson; Dirk Schadendorf; Matthias Mann; Iris Helfrich

doi:10.1002/ctm2.70094

Clinical and Translational Medicine ›› 2025, Vol. 15 ›› Issue (1) : e70094 DOI: 10.1002/ctm2.70094

RESEARCH ARTICLE

RECQL4 affects MHC class II-mediated signalling and favours an immune-evasive signature that limits response to immune checkpoint inhibitor therapy in patients with malignant melanoma

Author information +

¹. Department of Dermatology and Allergy, University Hospital of Munich, Ludwig-Maximilian-University, Munich, Germany

². German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany

³. Skin Cancer Unit of the Dermatology Department, Medical Faculty,West German Cancer Center, University Duisburg-Essen, Essen, Germany

⁴. German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, Essen, Germany

⁵. Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany

⁶. Lead Discovery Center GmbH, Dortmund, Germany

⁷. Department of Applied Computational Cancer Research, Institute for AI in Medicine (IKIM), University Hospital Essen, University Duisburg-Essen, Essen, Germany

⁸. Rudolf Schönheimer Institute of Biochemistry, Medical Faculty of the University of Leipzig, Leipzig, Germany

⁹. Biomolecular Spectroscopy and RUBiospec, NMR, Faculty of Chemistry and Biochemistry, Ruhr University of Bochum, Bochum, Germany

¹⁰. Center for Chromosome Stability, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen N, Denmark

Iris.Helfrich@med.uni-muenchen.de

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Abstract

	•High RECQL4 expression limits survival and can act as an independent prognostic factor in melanoma patients.
	•RECQL4 has the potential to act as a negative feedback mediator of immune checkpoint-targeted therapy by limiting signatures associated with therapeutic efficacy.
	•RECQL4 favours an immune-evasive phenotype by downregulating major histocompatibility complex class II molecules.

Keywords

immune evasion / immunotherapy / melanoma / MHC class II / RECQL4

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Sara Egea-Rodriguez,Renáta Váraljai,Thierry M. Nordmann,Restuan Lubis,Manuel Philip,Florian Rambow,Alexander Roesch,Michael Flaig,Susanne Horn,Raphael Stoll,Fang Zhao,Annette Paschen,Bert Klebl,Ian D. Hickson,Dirk Schadendorf,Matthias Mann,Iris Helfrich. RECQL4 affects MHC class II-mediated signalling and favours an immune-evasive signature that limits response to immune checkpoint inhibitor therapy in patients with malignant melanoma. Clinical and Translational Medicine, 2025, 15(1): e70094 DOI:10.1002/ctm2.70094

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2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.