Tumoral Interferon Beta Induces an Immune-Stimulatory Phenotype in Tumor-Associated Macrophages in Melanoma Brain Metastases.

Autor:	Gellert J; German Cancer Research Center (DKFZ) Heidelberg, Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, Heidelberg, Germany.; German Cancer Consortium (DKTK), DKFZ, Core Center Heidelberg, Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neuroscience (MCTN), Heidelberg University, Mannheim, Germany., Agardy DA; German Cancer Research Center (DKFZ) Heidelberg, Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, Heidelberg, Germany.; German Cancer Consortium (DKTK), DKFZ, Core Center Heidelberg, Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neuroscience (MCTN), Heidelberg University, Mannheim, Germany.; Faculty of Bioscience, Heidelberg University, Heidelberg, Germany., Kumar S; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Kourtesakis A; German Cancer Consortium (DKTK), DKFZ, Core Center Heidelberg, Heidelberg, Germany.; Faculty of Bioscience, Heidelberg University, Heidelberg, Germany.; German Cancer Research Center (DKFZ) Heidelberg, Clinical Cooperation Unit (CCU) Neurooncology, Heidelberg, Germany.; Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany., Boschert T; German Cancer Research Center (DKFZ) Heidelberg, Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, Heidelberg, Germany.; German Cancer Consortium (DKTK), DKFZ, Core Center Heidelberg, Heidelberg, Germany.; Helmholtz Institute for Translational Oncology Mainz (HI-TRON Mainz)-A Helmholtz Institute of the DKFZ, Mainz, Germany., Jähne K; German Cancer Research Center (DKFZ) Heidelberg, Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, Heidelberg, Germany.; German Cancer Consortium (DKTK), DKFZ, Core Center Heidelberg, Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neuroscience (MCTN), Heidelberg University, Mannheim, Germany., Breckwoldt MO; German Cancer Research Center (DKFZ) Heidelberg, Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, Heidelberg, Germany.; Department of Neuroradiology, Heidelberg University Hospital, Heidelberg University, Heidelberg, Germany., Bunse L; German Cancer Research Center (DKFZ) Heidelberg, Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, Heidelberg, Germany.; German Cancer Consortium (DKTK), DKFZ, Core Center Heidelberg, Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neuroscience (MCTN), Heidelberg University, Mannheim, Germany.; DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany.; Hertie Network of Excellence in Clinical Neuroscience, Frankfurt, Germany., Wick W; German Cancer Consortium (DKTK), DKFZ, Core Center Heidelberg, Heidelberg, Germany.; German Cancer Research Center (DKFZ) Heidelberg, Clinical Cooperation Unit (CCU) Neurooncology, Heidelberg, Germany.; Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany., Davies MA; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Platten M; German Cancer Research Center (DKFZ) Heidelberg, Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, Heidelberg, Germany.; German Cancer Consortium (DKTK), DKFZ, Core Center Heidelberg, Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neuroscience (MCTN), Heidelberg University, Mannheim, Germany.; Neurology Clinic and National Center for Tumor Diseases, University Hospital Heidelberg, Heidelberg, Germany.; Helmholtz Institute for Translational Oncology Mainz (HI-TRON Mainz)-A Helmholtz Institute of the DKFZ, Mainz, Germany.; DKFZ Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany.; Immune Monitoring Unit, National Center for Tumor Diseases (NCT), NCT Heidelberg, a partnership between DKFZ and University Hospital Heidelberg, Heidelberg, Germany., Bunse T; German Cancer Research Center (DKFZ) Heidelberg, Clinical Cooperation Unit (CCU) Neuroimmunology and Brain Tumor Immunology, Heidelberg, Germany.; German Cancer Consortium (DKTK), DKFZ, Core Center Heidelberg, Heidelberg, Germany.; Department of Neurology, Medical Faculty Mannheim, Mannheim Center for Translational Neuroscience (MCTN), Heidelberg University, Mannheim, Germany.
Jazyk:	angličtina
Zdroj:	Cancer research communications [Cancer Res Commun] 2024 Aug 01; Vol. 4 (8), pp. 2189-2202.
DOI:	10.1158/2767-9764.CRC-24-0024
Abstrakt:	Type I interferons (IFN) are immune-stimulatory cytokines involved in antiviral and antitumor immune responses. They enhance the efficacy of immunogenic anticancer therapies such as radiotherapy by activating both innate and adaptive immune cells. Macrophages are one of the most abundant innate immune cells in the immune microenvironment of melanoma brain metastases (MBM) and can exert potent immune-suppressive functions. Here, we investigate the potential of tumoral type I IFNs to repolarize tumor-associated macrophages (TAM) in two murine MBM models and assess the effects of radiotherapy-induced type I IFN on TAMs in a transcriptomic MBM patient dataset. In mice, we describe a proinflammatory M1-like TAM phenotype induced by tumoral IFNβ and identify a myeloid type I IFN-response signature associated with a high M1/M2-like TAM ratio. Following irradiation, patients with MBM displaying a myeloid type I IFN-response signature showed increased overall survival, providing evidence that tumoral IFNβ supports an effective antitumor immune response by re-educating immune-regulatory TAM. These findings uncover type I IFN-inducing therapies as a potential macrophage-targeting therapeutic approach and provide a rationale for combining radiotherapy with concomitant immunotherapy to improve treatment response in patients with MBM. Significance: Our study shows that re-education of tumor-associated macrophages by tumoral IFNβ translates into improved clinical outcome in patients with melanoma brain metastases, providing pathomechanistic insights into synergistic type I interferon-inducing therapies with immunotherapies and warranting investigation of IFNβ as a predictive biomarker for combined radioimmunotherapy. (©2024 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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