Midkine rewires the melanoma microenvironment toward a tolerogenic and immune-resistant state.

Animals B7-H1 Antigen / antagonists & inhibitors CD8-Positive T-Lymphocytes / drug effects Carcinogenesis / drug effects Gene Expression Regulation, Neoplastic / genetics Genetic Therapy Humans Melanoma, Experimental / genetics Mice Midkine / genetics NF-kappa B / genetics Programmed Cell Death 1 Receptor / antagonists & inhibitors Recombinant Proteins / genetics Transcriptome / genetics Tumor Microenvironment / genetics

Journal

Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015

Informations de publication

Date de publication:
12 2020
Historique:
received: 28 06 2019
accepted: 20 08 2020
pubmed: 21 10 2020
medline: 29 1 2021
entrez: 20 10 2020
Statut: ppublish

Résumé

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

Identifiants

DOI: 10.1038/s41591-020-1073-3 PMID: 33077955
pubmed: 33077955
doi: 10.1038/s41591-020-1073-3
pii: 10.1038/s41591-020-1073-3
doi:

Substances chimiques

B7-H1 Antigen 0
CD274 protein, human 0
MDK protein, human 0
NF-kappa B 0
Programmed Cell Death 1 Receptor 0
Recombinant Proteins 0
Midkine 137497-38-2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1865-1877

Commentaires et corrections

Type : CommentIn

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Auteurs

Daniela Cerezo-Wallis (D)

Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

Marta Contreras-Alcalde (M)

Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

Kevin Troulé (K)

Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

Xavier Catena (X)

Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

Cynthia Mucientes (C)

Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

Tonantzin G Calvo (TG)

Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

Estela Cañón (E)

Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

Cristina Tejedo (C)

Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

Paula C Pennacchi (PC)

Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

Sabrina Hogan (S)

Department of Dermatology, University of Zurich Hospital, Zurich, Switzerland.
ORCID: 0000-0003-3994-8109

Peter Kölblinger (P)

Department of Dermatology, University of Zurich Hospital, Zurich, Switzerland.

Héctor Tejero (H)

Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

Andrew X 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.

Nuria Ibarz (N)

Proteomics Unit, Biotechnology Programme, Spanish National Cancer Research Centre (CNIO) and ProteoRed-ISCIII, Madrid, Madrid, Spain.

Osvaldo Graña-Castro (O)

Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

Lola Martinez (L)

Proteomics Unit, Biotechnology Programme, Spanish National Cancer Research Centre (CNIO) and ProteoRed-ISCIII, Madrid, Madrid, Spain.

Javier Muñoz (J)

Flow Cytometry Unit, Biotechnology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Madrid, Spain.

Pablo Ortiz-Romero (P)

Dermatology Service, Hospital 12 de Octubre, Universidad Complutense Madrid Medical School, Madrid, Spain.
ORCID: 0000-0003-2985-9639

José L 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.

Gonzalo Gómez-López (G)

Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.

Fátima Al-Shahrour (F)

Bioinformatics Unit, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
ORCID: 0000-0003-2373-769X

Raúl 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.
ORCID: 0000-0001-7946-9255

Mitchell P Levesque (MP)

Department of Dermatology, University of Zurich Hospital, Zurich, Switzerland.

David Olmeda (D)

Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. dolmeda@cnio.es.
ORCID: 0000-0001-5513-5621

María S Soengas (MS)

Melanoma Laboratory, Molecular Oncology Programme, Spanish National Cancer Research Centre (CNIO), Madrid, Spain. msoengas@cnio.es.
ORCID: 0000-0003-0612-6299

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Midkine rewires the melanoma microenvironment...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Antigènes B7 › Antigène CD274 › Midkine rewires the melanoma microenvironment...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD8+ › Midkine rewires the melanoma microenvironment...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Processus néoplasiques › Carcinogenèse › Midkine rewires the melanoma microenvironment...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › Midkine rewires the melanoma microenvironment...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Génie génétique › Thérapie génétique › Midkine rewires the melanoma microenvironment...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Midkine rewires the melanoma microenvironment...
questionsmedicales.fr › Techniques d'investigation › Modèles animaux › Tumeurs expérimentales › Mélanome expérimental › Midkine rewires the melanoma microenvironment...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Midkine rewires the melanoma microenvironment...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Midkine › Midkine rewires the melanoma microenvironment...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteur de transcription NF-kappa B › Midkine rewires the melanoma microenvironment...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Antigènes de différenciation › Antigènes de différenciation des lymphocytes T › Récepteur-1 de mort cellulaire programmée › Midkine rewires the melanoma microenvironment...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines recombinantes › Midkine rewires the melanoma microenvironment...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Transcriptome › Midkine rewires the melanoma microenvironment...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › Midkine rewires the melanoma microenvironment...