Novel microenvironment-based classification of intrahepatic cholangiocarcinoma with therapeutic implications.

Humans Animals Mice Disease Models, Animal Proto-Oncogene Proteins p21(ras) / genetics Bile Duct Neoplasms / pathology Cholangiocarcinoma / pathology Bile Ducts, Intrahepatic / metabolism Tumor Microenvironment
cholangiocarcinoma gene expression immune response immunotherapy molecular biology

Journal

Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R

Informations de publication

Date de publication:
04 2023
Historique:
received: 08 11 2021
accepted: 03 05 2022
pmc-release: 01 04 2024
pubmed: 19 5 2022
medline: 10 3 2023
entrez: 18 5 2022
Statut: ppublish

Résumé

The diversity of the tumour microenvironment (TME) of intrahepatic cholangiocarcinoma (iCCA) has not been comprehensively assessed. We aimed to generate a novel molecular iCCA classifier that incorporates elements of the stroma, tumour and immune microenvironment ('STIM' classification). We applied virtual deconvolution to transcriptomic data from ~900 iCCAs, enabling us to devise a novel classification by selecting for the most relevant TME components. Murine models were generated through hydrodynamic tail vein injection and compared with the human disease. iCCA is composed of five robust STIM classes encompassing both inflamed (35%) and non-inflamed profiles (65%). The inflamed classes, named We describe a comprehensive TME-based stratification of iCCA. Cross-species analysis establishes murine models that align closely to human iCCA for the preclinical testing of combination strategies.

Identifiants

DOI: 10.1136/gutjnl-2021-326514 PMID: 35584893 PMC: PMC10388405
pubmed: 35584893
pii: gutjnl-2021-326514
doi: 10.1136/gutjnl-2021-326514
pmc: PMC10388405
mid: NIHMS1911147
doi:

Substances chimiques

Proto-Oncogene Proteins p21(ras) EC 3.6.5.2

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

736-748

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK056621
Pays : United States
Organisme : Cancer Research UK
ID : 26813
Pays : United Kingdom
Organisme : NIGMS NIH HHS
ID : T32 GM062754
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM146636
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK128289
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA078207
Pays : United States
Organisme : NCI NIH HHS
ID : R37 CA230636
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007280
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI078892
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA196521
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: JML is receiving research support from Bayer HealthCare Pharmaceuticals, Eisai Inc, Bristol-Myers Squibb, Boehringer-Ingelheim and Ipsen, and consulting fees from Eli Lilly, Bayer HealthCare Pharmaceuticals, Bristol-Myers Squibb, Eisai Inc, Celsion Corporation, Exelixis, Merck, Ipsen, Genentech, Roche, Glycotest, Nucleix, Sirtex, Mina Alpha Ltd and AstraZeneca. AV has received consulting fees from Genentech, Guidepoint, Fujifilm, Boehringer Ingelheim, FirstWord, and MHLife Sciences; advisory board fees from Exact Sciences, Nucleix, Gilead and NGM Pharmaceuticals; and research support from Eisai.

Références

Nat Genet. 2015 Sep;47(9):1003-10
pubmed: 26258846
EMBO J. 2010 Dec 1;29(23):3952-66
pubmed: 20959807
Nat Rev Gastroenterol Hepatol. 2020 Sep;17(9):557-588
pubmed: 32606456
Cancer Cell. 2022 Jan 10;40(1):70-87.e15
pubmed: 34971568
Transl Cancer Res. 2019 Mar;8(Suppl 2):S167-S170
pubmed: 30956952
BMC Cancer. 2019 Oct 16;19(1):963
pubmed: 31619201
Future Oncol. 2020 Oct;16(30):2375-2384
pubmed: 32580579
Biochem Cell Biol. 2018 Oct;96(5):619-626
pubmed: 29316404
J Clin Invest. 2012 Aug;122(8):2911-5
pubmed: 22797301
Int J Cancer. 2020 Oct 15;147(8):2190-2198
pubmed: 32359091
Cell. 2014 Jun 5;157(6):1324-1338
pubmed: 24906150
Lancet Oncol. 2020 Aug;21(8):e371
pubmed: 32758466
Cancer Cell. 2020 Oct 12;38(4):500-515.e3
pubmed: 32916126
Nature. 2018 Nov;563(7731):347-353
pubmed: 30429548
Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4164-9
pubmed: 15016911
J Pathol. 2020 Apr;250(4):420-439
pubmed: 31960425
J Hepatol. 2020 Nov;73(5):1118-1130
pubmed: 32505533
Cell Rep. 2017 Jun 27;19(13):2878-2880
pubmed: 28658632
Gastroenterology. 2009 Mar;136(3):1012-24
pubmed: 19150350
Hepatology. 2012 Nov;56(5):1792-803
pubmed: 22707408
Nat Genet. 2006 May;38(5):500-1
pubmed: 16642009
Oncogene. 2018 Jun;37(24):3229-3242
pubmed: 29545603
Front Immunol. 2020 Apr 22;11:720
pubmed: 32391018
J Hepatol. 2020 Aug;73(2):315-327
pubmed: 32173382
PLoS One. 2012;7(6):e38972
pubmed: 22701738
Gastroenterology. 2013 Apr;144(4):829-40
pubmed: 23295441
JHEP Rep. 2019 Jul 10;1(4):297-311
pubmed: 32039381
Cell. 2016 Mar 24;165(1):35-44
pubmed: 26997480
Nat Genet. 2015 Apr;47(4):320-9
pubmed: 25706628
Liver Int. 2019 May;39 Suppl 1:19-31
pubmed: 30851228
J Hepatol. 2019 Oct;71(4):742-752
pubmed: 31195063
Nat Rev Mol Cell Biol. 2019 Feb;20(2):69-84
pubmed: 30459476
Gut. 2023 Jan;72(1):129-140
pubmed: 35197323
Nature. 2014 Nov 27;515(7528):563-7
pubmed: 25428504
Lancet Oncol. 2020 May;21(5):671-684
pubmed: 32203698
Nat Genet. 2015 Oct;47(10):1168-78
pubmed: 26343385
Cancer Discov. 2017 Oct;7(10):1116-1135
pubmed: 28667006
Cell. 2018 Sep 6;174(6):1586-1598.e12
pubmed: 30100188
Gastroenterology. 2017 Sep;153(3):812-826
pubmed: 28624577
Cancer Cell. 2021 Jun 14;39(6):866-882.e11
pubmed: 33930309
Cancer Discov. 2018 Mar;8(3):304-319
pubmed: 29196464
J Clin Invest. 2006 Jun;116(6):1561-70
pubmed: 16741576
Cancer Cell. 2020 Jan 13;37(1):37-54.e9
pubmed: 31883968
Blood. 2004 Nov 15;104(10):3198-204
pubmed: 15271796
Cancer Cell. 2015 Dec 14;28(6):690-714
pubmed: 26678337
Hepatology. 2020 Sep;72(3):965-981
pubmed: 31875970
Cancer Discov. 2021 Jan;11(1):142-157
pubmed: 32816843
Immunity. 2018 Mar 20;48(3):399-416
pubmed: 29562192
Proc Natl Acad Sci U S A. 2021 May 11;118(19):
pubmed: 33941680
Nat Commun. 2018 Nov 8;9(1):4692
pubmed: 30410077
Cancer Discov. 2020 Sep;10(9):1330-1351
pubmed: 32434947
Gastroenterology. 2012 Apr;142(4):1021-1031.e15
pubmed: 22178589
Clin Cancer Res. 2021 Sep 1;27(17):4669-4679
pubmed: 33827891
Cell Res. 2020 Jun;30(6):507-519
pubmed: 32467593

Auteurs

Miguel A Martin-Serrano (MA)

Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Benjamin Kepecs (B)

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Miguel Torres-Martin (M)

Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Catalunya, Spain.

Emily R Bramel (ER)

Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Philipp K Haber (PK)

Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Elliot Merritt (E)

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
The Precision Immunology Institute (PrIISM), Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Alexander Rialdi (A)

Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Nesteene Joy Param (NJ)

Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Miho Maeda (M)

Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Katherine E Lindblad (KE)

Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
The Precision Immunology Institute (PrIISM), Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

James K Carter (JK)

Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Marina Barcena-Varela (M)

Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
The Precision Immunology Institute (PrIISM), Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Vincenzo Mazzaferro (V)

General Surgery and Liver Transplantation Unit, Department of Oncology and Hemato-Oncology, University of Milan and Istituto Nazionale Tumori, IRCCS Foundation, Milano, Lombardia, Italy.

Myron Schwartz (M)

Department of Surgery, Tisch Cancer Institute, Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Silvia Affo (S)

Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Catalunya, Spain.

Robert F Schwabe (RF)

Department of Medicine, Columbia University, New York, New York, USA.

Augusto Villanueva (A)

Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Ernesto Guccione (E)

Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Scott L Friedman (SL)

Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
ORCID: 0000-0003-1178-6195

Amaia Lujambio (A)

Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
The Precision Immunology Institute (PrIISM), Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Department of Oncological Sciences, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
ORCID: 0000-0002-2798-1481

Anna Tocheva (A)

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
The Precision Immunology Institute (PrIISM), Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Josep M Llovet (JM)

Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Translational Research in Hepatic Oncology, Liver Unit, IDIBAPS, Hospital Clinic, University of Barcelona, Barcelona, Catalunya, Spain.
Institució Catalana de Recerca i Estudis Avançats, Barcelona, Spain.

Swan N Thung (SN)

Department of Pathology, Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Alexander M Tsankov (AM)

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

Daniela Sia (D)

Division of Liver Diseases, Department of Medicine, Tisch Cancer Institute, Liver Cancer Program, Icahn School of Medicine at Mount Sinai, New York, New York, USA daniela.sia@mssm.edu.
ORCID: 0000-0002-9000-611X

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Novel microenvironment-based classification of...
Recherchemedicale.com › Eucaryotes › Animaux › Novel microenvironment-based classification of...
Recherchemedicale.com › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Novel microenvironment-based classification of...
Recherchemedicale.com › Techniques d'investigation › Modèles théoriques › Modèles biologiques › Modèles animaux de maladie humaine › Novel microenvironment-based classification of...
Recherchemedicale.com › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines oncogènes › Protéines proto-oncogènes › Protéines proto-oncogènes p21(ras) › Novel microenvironment-based classification of...
Recherchemedicale.com › Maladies de l'appareil digestif › Tumeurs de l'appareil digestif › Tumeurs des voies biliaires › Tumeurs des canaux biliaires › Novel microenvironment-based classification of...
Recherchemedicale.com › Tumeurs › Tumeurs par type histologique › Tumeurs épithéliales épidermoïdes et glandulaires › Carcinomes › Adénocarcinome › Cholangiocarcinome › Novel microenvironment-based classification of...
Recherchemedicale.com › Système digestif › Foie › Conduits biliaires intrahépatiques › Novel microenvironment-based classification of...
Recherchemedicale.com › Phénomènes physiologiques cellulaires › Microenvironnement cellulaire › Microenvironnement tumoral › Novel microenvironment-based classification of...