Targeting tumour-associated macrophages in hodgkin lymphoma using engineered extracellular matrix-mimicking cryogels.

Humans Tumor-Associated Macrophages / metabolism Hodgkin Disease / drug therapy Cryogels p38 Mitogen-Activated Protein Kinases / metabolism Extracellular Matrix / metabolism
Drug screening Extracellular matrix Hodgkin lymphoma Invasion Ruxolitinib Tumour-associated macrophages

Journal

Biomaterials
ISSN: 1878-5905
Titre abrégé: Biomaterials
Pays: Netherlands
ID NLM: 8100316

Informations de publication

Date de publication:
06 2023
Historique:
received: 03 11 2022
revised: 08 03 2023
accepted: 06 04 2023
medline: 15 5 2023
pubmed: 20 4 2023
entrez: 19 04 2023
Statut: ppublish

Résumé

Tumour-associated macrophages are linked with poor prognosis and resistance to therapy in Hodgkin lymphoma; however, there are no suitable preclinical models to identify macrophage-targeting therapeutics. We used primary human tumours to guide the development of a mimetic cryogel, wherein Hodgkin (but not Non-Hodgkin) lymphoma cells promoted primary human macrophage invasion. In an invasion inhibitor screen, we identified five drug hits that significantly reduced tumour-associated macrophage invasion: marimastat, batimastat, AS1517499, ruxolitinib, and PD-169316. Importantly, ruxolitinib has demonstrated recent success in Hodgkin lymphoma clinical trials. Both ruxolitinib and PD-169316 (a p38 mitogen-activated protein kinase (p38 MAPK) inhibitor) decreased the percent of M2-like macrophages; however, only PD-169316 enhanced the percentage of M1-like macrophages. We validated p38 MAPK as an anti-invasion drug target with five additional drugs using a high-content imaging platform. With our biomimetic cryogel, we modeled macrophage invasion in Hodgkin lymphoma and then used it for target discovery and drug screening, ultimately identifying potential future therapeutics.

Identifiants

DOI: 10.1016/j.biomaterials.2023.122121 PMID: 37075613
pubmed: 37075613
pii: S0142-9612(23)00129-1
doi: 10.1016/j.biomaterials.2023.122121
pii:
doi:

Substances chimiques

ruxolitinib 82S8X8XX8H
Cryogels 0
p38 Mitogen-Activated Protein Kinases EC 2.7.11.24

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

122121

Subventions

Organisme : CIHR
Pays : Canada

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Anne L Partel reports a relationship with Pathcore that includes: equity or stocks.

Auteurs

Laura C Bahlmann (LC)

Institute of Biomedical Engineering, 164 College Street, Toronto, Ontario, M5S 3G9, Canada; The Donnelly Centre, University of Toronto, Toronto, 160 College St, Ontario, M5S 3E1, Canada.

Chang Xue (C)

Institute of Biomedical Engineering, 164 College Street, Toronto, Ontario, M5S 3G9, Canada; The Donnelly Centre, University of Toronto, Toronto, 160 College St, Ontario, M5S 3E1, Canada.

Allysia A Chin (AA)

The Donnelly Centre, University of Toronto, Toronto, 160 College St, Ontario, M5S 3E1, Canada; Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario, M5S 3E5, Canada.

Arianna Skirzynska (A)

Institute of Biomedical Engineering, 164 College Street, Toronto, Ontario, M5S 3G9, Canada; The Donnelly Centre, University of Toronto, Toronto, 160 College St, Ontario, M5S 3E1, Canada; Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario, M5S 3E5, Canada.

Joy Lu (J)

Institute of Biomedical Engineering, 164 College Street, Toronto, Ontario, M5S 3G9, Canada; The Donnelly Centre, University of Toronto, Toronto, 160 College St, Ontario, M5S 3E1, Canada.

Brigitte Thériault (B)

Drug Discovery Program, Ontario Institute of Cancer Research, 661 University Ave Suite 510, Toronto, Ontario, M5G 0A3, Canada.

David Uehling (D)

Drug Discovery Program, Ontario Institute of Cancer Research, 661 University Ave Suite 510, Toronto, Ontario, M5G 0A3, Canada.

Yulia Yerofeyeva (Y)

Biomarker Imaging Research Laboratory, Sunnybrook Research Institute, 2075 Bayview Ave, Toronto, Ontario, M4N 3M5, Canada.

Rachel Peters (R)

Biomarker Imaging Research Laboratory, Sunnybrook Research Institute, 2075 Bayview Ave, Toronto, Ontario, M4N 3M5, Canada.

Kela Liu (K)

Biomarker Imaging Research Laboratory, Sunnybrook Research Institute, 2075 Bayview Ave, Toronto, Ontario, M4N 3M5, Canada.

Jianan Chen (J)

Department of Medical Biophysics, University of Toronto, 101 College St Suite 15-701, Toronto, Ontario, M5G 1L7, Canada.

Anne L Martel (AL)

Department of Medical Biophysics, University of Toronto, 101 College St Suite 15-701, Toronto, Ontario, M5G 1L7, Canada; Physical Sciences, Odette Cancer Research Program, Sunnybrook Research Institute, 2075 Bayview Ave, Toronto, Ontario, M4N 3M5, Canada.

Martin Yaffe (M)

Department of Medical Biophysics, University of Toronto, 101 College St Suite 15-701, Toronto, Ontario, M5G 1L7, Canada; Physical Sciences, Odette Cancer Research Program, Sunnybrook Research Institute, 2075 Bayview Ave, Toronto, Ontario, M4N 3M5, Canada.

Rima Al-Awar (R)

Drug Discovery Program, Ontario Institute of Cancer Research, 661 University Ave Suite 510, Toronto, Ontario, M5G 0A3, Canada; Department of Pharmacology & Toxicology, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada.

Rashmi S Goswami (RS)

Biological Sciences, Odette Cancer Research Program, Sunnybrook Research Institute, 2075 Bayview Ave, Toronto, Ontario, M4N 3M5, Canada; Department of Laboratory Medicine and Molecular Diagnostics, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, Ontario, M4N 3M5, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.

Jarkko Ylanko (J)

Biological Sciences, Odette Cancer Research Program, Sunnybrook Research Institute, 2075 Bayview Ave, Toronto, Ontario, M4N 3M5, Canada.

David W Andrews (DW)

Department of Medical Biophysics, University of Toronto, 101 College St Suite 15-701, Toronto, Ontario, M5G 1L7, Canada; Biological Sciences, Odette Cancer Research Program, Sunnybrook Research Institute, 2075 Bayview Ave, Toronto, Ontario, M4N 3M5, Canada; Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, Ontario, M5S 1A8, Canada.

John Kuruvilla (J)

Princess Margaret Cancer Centre, University Health Network, 610 University Ave, Toronto, Ontario, M5G 2C1, Canada.

Rob C Laister (RC)

Princess Margaret Cancer Centre, University Health Network, 610 University Ave, Toronto, Ontario, M5G 2C1, Canada. Electronic address: Rob.Laister@uhnresearch.ca.

Molly S Shoichet (MS)

Institute of Biomedical Engineering, 164 College Street, Toronto, Ontario, M5S 3G9, Canada; The Donnelly Centre, University of Toronto, Toronto, 160 College St, Ontario, M5S 3E1, Canada; Department of Chemical Engineering and Applied Chemistry, University of Toronto, 200 College Street, Toronto, Ontario, M5S 3E5, Canada; Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6, Canada. Electronic address: molly.shoichet@utoronto.ca.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Targeting tumour-associated macrophages in...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Phagocytes › Macrophages › Macrophages associés aux tumeurs › Targeting tumour-associated macrophages in...
questionsmedicales.fr › Maladies du système immunitaire › Syndromes immunoprolifératifs › Syndromes lymphoprolifératifs › Lymphomes › Maladie de Hodgkin › Targeting tumour-associated macrophages in...
questionsmedicales.fr › Préparations pharmaceutiques › Colloïdes › Gels › Hydrogels › Cryogels › Targeting tumour-associated macrophages in...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Mitogen-Activated Protein Kinases › p38 Mitogen-Activated Protein Kinases › Targeting tumour-associated macrophages in...
questionsmedicales.fr › Cellules › Structures cellulaires › Espace extracellulaire › Matrice extracellulaire › Targeting tumour-associated macrophages in...