دورية أكاديمية
Midkine rewires the melanoma microenvironment toward a tolerogenic and immune-resistant state.
| العنوان: | Midkine rewires the melanoma microenvironment toward a tolerogenic and immune-resistant state. |
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| المؤلفون: | Cerezo-Wallis D; Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Contreras-Alcalde M; Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Troulé K; Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Catena X; Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Mucientes C; Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Calvo TG; Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Cañón E; Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Tejedo C; Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Pennacchi PC; Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Hogan S; Department of Dermatology, University of Zurich Hospital, Zurich, Switzerland., Kölblinger P; Department of Dermatology, University of Zurich Hospital, Zurich, Switzerland., Tejero H; Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Chen AX; Program for Mathematical Genomics, Departament of Systems Biology, Departament of Biomedical Informatics, Columbia University College of Physicians and Surgeons, New York, NY, USA., Ibarz N; Proteomics Unit, Biotechnology Programme, Spanish National Cancer Research Centre (CNIO) and ProteoRed-ISCIII, Madrid, Madrid, Spain., Graña-Castro O; Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Martinez L; Proteomics Unit, Biotechnology Programme, Spanish National Cancer Research Centre (CNIO) and ProteoRed-ISCIII, Madrid, Madrid, Spain., Muñoz J; Flow Cytometry Unit, Biotechnology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Madrid, Spain., Ortiz-Romero P; Dermatology Service, Hospital 12 de Octubre, Universidad Complutense Madrid Medical School, Madrid, Spain., Rodriguez-Peralto JL; Instituto de Investigación i+12, Hospital 12 de Octubre, Universidad Complutense Madrid Medical School, Madrid, Spain.; Pathology Service, Hospital 12 de Octubre, Universidad Complutense Madrid Medical School, Madrid, Spain., Gómez-López G; Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Al-Shahrour F; Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain., Rabadán R; Program for Mathematical Genomics, Departament of Systems Biology, Departament of Biomedical Informatics, Columbia University College of Physicians and Surgeons, New York, NY, USA., Levesque MP; Department of Dermatology, University of Zurich Hospital, Zurich, Switzerland., Olmeda D; Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. dolmeda@cnio.es., Soengas MS; Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. msoengas@cnio.es. |
| المصدر: | Nature medicine [Nat Med] 2020 Dec; Vol. 26 (12), pp. 1865-1877. Date of Electronic Publication: 2020 Oct 19. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature Publishing Company Country of Publication: United States NLM ID: 9502015 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-170X (Electronic) Linking ISSN: 10788956 NLM ISO Abbreviation: Nat Med Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York Ny : Nature Publishing Company Original Publication: New York, NY : Nature Pub. Co., [1995- |
| مواضيع طبية MeSH: | Carcinogenesis/*drug effects , Melanoma, Experimental/*therapy , Midkine/*genetics , Tumor Microenvironment/*genetics, Animals ; B7-H1 Antigen/antagonists & inhibitors ; B7-H1 Antigen/genetics ; CD8-Positive T-Lymphocytes/drug effects ; Gene Expression Regulation, Neoplastic/genetics ; Genetic Therapy ; Humans ; Melanoma, Experimental/genetics ; Melanoma, Experimental/pathology ; Mice ; Midkine/pharmacology ; NF-kappa B/genetics ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Programmed Cell Death 1 Receptor/genetics ; Recombinant Proteins/genetics ; Recombinant Proteins/pharmacology ; Transcriptome/genetics |
| مستخلص: | An open question in aggressive cancers such as melanoma is how malignant cells can shift the immune system to pro-tumorigenic functions. Here we identify midkine (MDK) as a melanoma-secreted driver of an inflamed, but immune evasive, microenvironment that defines poor patient prognosis and resistance to immune checkpoint blockade. Mechanistically, MDK was found to control the transcriptome of melanoma cells, allowing for coordinated activation of nuclear factor-κB and downregulation of interferon-associated pathways. The resulting MDK-modulated secretome educated macrophages towards tolerant phenotypes that promoted CD8 + T cell dysfunction. In contrast, genetic targeting of MDK sensitized melanoma cells to anti-PD-1/anti-PD-L1 treatment. Emphasizing the translational relevance of these findings, the expression profile of MDK-depleted tumors was enriched in key indicators of a good response to immune checkpoint blockers in independent patient cohorts. Together, these data reveal that MDK acts as an internal modulator of autocrine and paracrine signals that maintain immune suppression in aggressive melanomas. |
| التعليقات: | Comment in: Nat Rev Cancer. 2021 Jan;21(1):4. (PMID: 33168967) |
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| المشرفين على المادة: | 0 (B7-H1 Antigen) 0 (CD274 protein, human) 0 (MDK protein, human) 0 (NF-kappa B) 0 (Programmed Cell Death 1 Receptor) 0 (Recombinant Proteins) 137497-38-2 (Midkine) |
| تواريخ الأحداث: | Date Created: 20201020 Date Completed: 20210128 Latest Revision: 20220804 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1038/s41591-020-1073-3 |
| PMID: | 33077955 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1546-170X |
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| DOI: | 10.1038/s41591-020-1073-3 |