Tankyrase inhibition sensitizes melanoma to PD-1 immune checkpoint blockade in syngeneic mouse models.

Adaptor Proteins, Signal Transducing / genetics Animals Antineoplastic Combined Chemotherapy Protocols / pharmacology CD8-Positive T-Lymphocytes / drug effects Cytotoxicity, Immunologic / drug effects Drug Synergism Enzyme Inhibitors / pharmacology Female HEK293 Cells Humans Immune Checkpoint Inhibitors / pharmacology Interferon-gamma / metabolism Lymphocytes, Tumor-Infiltrating / drug effects Melanoma, Experimental / drug therapy Mice, Inbred C57BL Mice, Inbred DBA Mice, Transgenic Programmed Cell Death 1 Receptor / antagonists & inhibitors Skin Neoplasms / drug therapy Sulfones / pharmacology Tankyrases / antagonists & inhibitors Triazoles / pharmacology Tumor Burden / drug effects Wnt Signaling Pathway / drug effects YAP-Signaling Proteins beta Catenin / genetics

Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
24 04 2020
Historique:
received: 01 12 2018
accepted: 26 03 2020
entrez: 26 4 2020
pubmed: 26 4 2020
medline: 16 6 2021
Statut: epublish

Résumé

The development of immune checkpoint inhibitors represents a major breakthrough in cancer therapy. Nevertheless, a substantial number of patients fail to respond to checkpoint pathway blockade. Evidence for WNT/β-catenin signaling-mediated immune evasion is found in a subset of cancers including melanoma. Currently, there are no therapeutic strategies available for targeting WNT/β-catenin signaling. Here we show that a specific small-molecule tankyrase inhibitor, G007-LK, decreases WNT/β-catenin and YAP signaling in the syngeneic murine B16-F10 and Clone M-3 melanoma models and sensitizes the tumors to anti-PD-1 immune checkpoint therapy. Mechanistically, we demonstrate that the synergistic effect of tankyrase and checkpoint inhibitor treatment is dependent on loss of β-catenin in the tumor cells, anti-PD-1-stimulated infiltration of T cells into the tumor and induction of an IFNγ- and CD8

Identifiants

DOI: 10.1038/s42003-020-0916-2 PMID: 32332858 PMC: PMC7181813
pubmed: 32332858
doi: 10.1038/s42003-020-0916-2
pii: 10.1038/s42003-020-0916-2
pmc: PMC7181813
doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0
CTNNB1 protein, mouse 0
Enzyme Inhibitors 0
G007-LK 0
IFNG protein, mouse 0
Immune Checkpoint Inhibitors 0
Pdcd1 protein, mouse 0
Programmed Cell Death 1 Receptor 0
Sulfones 0
Triazoles 0
YAP-Signaling Proteins 0
Yap1 protein, mouse 0
beta Catenin 0
Interferon-gamma 82115-62-6
Tankyrases EC 2.4.2.30

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

196

Références

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Auteurs

Jo Waaler (J)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950, Nydalen, 0424, Oslo, Norway. jo.waaler@rr-research.no.
Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110, Blindern, 0317, Oslo, Norway. jo.waaler@rr-research.no.
ORCID: 0000-0002-8501-6225

Line Mygland (L)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950, Nydalen, 0424, Oslo, Norway.
Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110, Blindern, 0317, Oslo, Norway.

Anders Tveita (A)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950, Nydalen, 0424, Oslo, Norway.
K. G. Jebsen Centre for B cell malignancies, Oslo University Hospital, P.O. Box 4950, Nydalen, 0424, Oslo, Norway.
ORCID: 0000-0002-0668-9262

Martin Frank Strand (MF)

School of Health Sciences, Kristiania University College, P.O. Box 1190, Sentrum, 0107, Oslo, Norway.
ORCID: 0000-0002-2588-5488

Nina Therese Solberg (NT)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950, Nydalen, 0424, Oslo, Norway.
Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110, Blindern, 0317, Oslo, Norway.

Petter Angell Olsen (PA)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950, Nydalen, 0424, Oslo, Norway.
Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110, Blindern, 0317, Oslo, Norway.

Aleksandra Aizenshtadt (A)

Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110, Blindern, 0317, Oslo, Norway.

Marte Fauskanger (M)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950, Nydalen, 0424, Oslo, Norway.
K. G. Jebsen Centre for B cell malignancies, Oslo University Hospital, P.O. Box 4950, Nydalen, 0424, Oslo, Norway.

Kaja Lund (K)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950, Nydalen, 0424, Oslo, Norway.
Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110, Blindern, 0317, Oslo, Norway.

Shoshy Alam Brinch (SA)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950, Nydalen, 0424, Oslo, Norway.
Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110, Blindern, 0317, Oslo, Norway.

Max Lycke (M)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950, Nydalen, 0424, Oslo, Norway.
Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110, Blindern, 0317, Oslo, Norway.

Elisabeth Dybing (E)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950, Nydalen, 0424, Oslo, Norway.
Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110, Blindern, 0317, Oslo, Norway.

Vegard Nygaard (V)

Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, P.O. Box 4953, Nydalen, 0424, Oslo, Norway.

Sigurd Læines Bøe (SL)

Department of Medical Biochemistry, Oslo University Hospital, Radiumhospitalet, Ullernchausseen 70, 0379, Oslo, Norway.

Karen-Marie Heintz (KM)

Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, P.O. Box 4953, Nydalen, 0424, Oslo, Norway.

Eivind Hovig (E)

Department of Tumor Biology, Institute for Cancer Research, Oslo University Hospital, P.O. Box 4953, Nydalen, 0424, Oslo, Norway.
Center of Bioinformatics, Department of Informatics, University of Oslo, P.O. Box 1080, Blindern, 0316, Oslo, Norway.
ORCID: 0000-0002-9103-1077

Clara Hammarström (C)

Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. box 4950, Nydalen, 0424, Oslo, Norway.

Alexandre Corthay (A)

Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110, Blindern, 0317, Oslo, Norway.
Department of Pathology, Oslo University Hospital, Rikshospitalet, P.O. box 4950, Nydalen, 0424, Oslo, Norway.
ORCID: 0000-0001-9519-5725

Stefan Krauss (S)

Department of Immunology and Transfusion Medicine, Oslo University Hospital, P.O. Box 4950, Nydalen, 0424, Oslo, Norway.
Hybrid Technology Hub - Centre of Excellence, Institute of Basic Medical Sciences, University of Oslo, P.O. Box 1110, Blindern, 0317, Oslo, Norway.

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Eucaryotes › Animaux › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Association de médicaments › Protocoles de polychimiothérapie antinéoplasique › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD8+ › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Phénomènes du système immunitaire › Cytotoxicité immunologique › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Interactions médicamenteuses › Synergie des médicaments › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Cellules › Cellules épithéliales › Cellules HEK293 › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Antinéoplasiques immunologiques › Inhibiteurs de points de contrôle immunitaires › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Lymphokines › Facteurs d'activation des macrophages › Interféron gamma › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes TIL › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Techniques d'investigation › Modèles animaux › Tumeurs expérimentales › Mélanome expérimental › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée C57BL › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée DBA › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Antigènes de différenciation › Antigènes de différenciation des lymphocytes T › Récepteur-1 de mort cellulaire programmée › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Tumeurs cutanées › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Composés chimiques organiques › Composés du soufre › Sulfones › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › Glycosyltransferase › Pentosyltransferases › ADP ribose transferases › Poly(ADP-ribose) polymerases › Tankyrases › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Composés hétérocycliques › Composés hétéromonocycliques › Azoles › Triazoles › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Techniques d'investigation › Charge tumorale › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Voie de signalisation Wnt › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protéines adaptatrices de la transduction du signal › Protéines de signalisation YAP › Tankyrase inhibition sensitizes melanoma to...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › bêta-Caténine › Tankyrase inhibition sensitizes melanoma to...