Preclinical validation of Alpha-Enolase (ENO1) as a novel immunometabolic target in multiple myeloma.

Antineoplastic Combined Chemotherapy Protocols / pharmacology B7-H1 Antigen / antagonists & inhibitors Biomarkers, Tumor / antagonists & inhibitors Cell Communication / drug effects Cell Culture Techniques Coculture Techniques DNA-Binding Proteins / antagonists & inhibitors Dendritic Cells / drug effects Gene Expression Profiling Glycolysis / drug effects Histone Deacetylase 6 / antagonists & inhibitors Histone Deacetylase Inhibitors / pharmacology Humans Killer Cells, Natural / immunology Lymphocyte Activation / drug effects Multiple Myeloma / drug therapy Phosphopyruvate Hydratase / antagonists & inhibitors Primary Cell Culture T-Lymphocytes, Cytotoxic / immunology Tumor Cells, Cultured Tumor Suppressor Proteins / antagonists & inhibitors

Journal

Oncogene
ISSN: 1476-5594
Titre abrégé: Oncogene
Pays: England
ID NLM: 8711562

Informations de publication

Date de publication:
03 2020
Historique:
received: 04 11 2019
accepted: 20 01 2020
revised: 07 01 2020
pubmed: 7 2 2020
medline: 15 12 2020
entrez: 7 2 2020
Statut: ppublish

Résumé

Bone marrow plasmacytoid dendritic cells (pDCs) in patients with multiple myeloma (MM) promote tumor growth, survival, drug resistance, and immune suppression. Understanding the molecular signaling crosstalk among the tumor cells, pDCs and immune cells will identify novel therapeutic approaches to enhance anti-MM immunity. Using oligonucleotide arrays, we found that pDC-MM interactions induce metabolic enzyme Alpha-Enolase (ENO1) in both pDCs and MM cells. Analysis of MM patient gene expression profiling database showed that ENO1 expression inversely correlates with overall survival. Protein expression analysis showed that ENO1 is expressed in pDC and MM cells; and importantly, that pDC-MM coculture further increases ENO1 expression in both MM cells and pDCs. Using our coculture models of patient autologous pDC-T-NK-MM cells, we examined whether targeting ENO1 can enhance anti-MM immunity. Biochemical inhibition of ENO1 with ENO1 inhibitor (ENO1i) activates pDCs, as well as increases pDC-induced MM-specific CD8

Identifiants

DOI: 10.1038/s41388-020-1172-0 PMID: 32024967 PMC: PMC7132141
pubmed: 32024967
doi: 10.1038/s41388-020-1172-0
pii: 10.1038/s41388-020-1172-0
pmc: PMC7132141
mid: NIHMS1574464
doi:

Substances chimiques

B7-H1 Antigen 0
Biomarkers, Tumor 0
CD274 protein, human 0
DNA-Binding Proteins 0
Histone Deacetylase Inhibitors 0
Tumor Suppressor Proteins 0
HDAC6 protein, human EC 3.5.1.98
Histone Deacetylase 6 EC 3.5.1.98
ENO1 protein, human EC 4.2.1.11
Phosphopyruvate Hydratase EC 4.2.1.11

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

2786-2796

Subventions

Organisme : NCI NIH HHS
ID : P01 CA155258
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA100707
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA050947
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA207237
Pays : United States

Commentaires et corrections

Type : ErratumIn

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Auteurs

Arghya Ray (A)

Department of Medical Oncology, The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Yan Song (Y)

Department of Medical Oncology, The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Ting Du (T)

Department of Medical Oncology, The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Dharminder Chauhan (D)

Department of Medical Oncology, The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Dharminder_Chauhan@dfci.harvard.edu.

Kenneth C Anderson (KC)

Department of Medical Oncology, The LeBow Institute for Myeloma Therapeutics and Jerome Lipper Myeloma Center, Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Kenneth_Anderson@dfci.harvard.edu.

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Classifications MeSH

questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Association de médicaments › Protocoles de polychimiothérapie antinéoplasique › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Antigènes B7 › Antigène CD274 › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Communication cellulaire › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de culture cellulaire › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de coculture › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de liaison à l'ADN › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Système phagocytaire mononucléé › Cellules dendritiques › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de profil d'expression de gènes › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Métabolisme › Voies et réseaux métaboliques › Glycolyse › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Amidohydrolases › Histone deacetylases › Histone deacetylase 6 › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Mécanismes moléculaires de l'action pharmacologique › Antienzymes › Inhibiteurs de désacétylase d'histone › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Cellules tueuses naturelles › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Phénomènes du système immunitaire › Activation des lymphocytes › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Maladies du système immunitaire › Syndromes immunoprolifératifs › Paraprotéinémies › Myélome multiple › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Lyases › Carbon-oxygen lyases › Hydro-lyases › Enolase › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Techniques d'investigation › Techniques in vitro › Techniques de culture › Techniques de culture cellulaire › Culture de cellules primaires › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Sous-populations de lymphocytes T › Lymphocytes T cytotoxiques › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Preclinical validation of Alpha-Enolase (ENO1)...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Preclinical validation of Alpha-Enolase (ENO1)...