Interplay of somatic alterations and immune infiltration modulates response to PD-1 blockade in advanced clear cell renal cell carcinoma.

Adult Aged Aged, 80 and over Antigen Presentation / genetics Antineoplastic Agents, Immunological / therapeutic use CD8-Positive T-Lymphocytes / immunology Carcinoma, Renal Cell / drug therapy Chromosome Deletion Chromosomes, Human, Pair 6 Chromosomes, Human, Pair 9 / genetics Class I Phosphatidylinositol 3-Kinases / genetics DNA-Binding Proteins / genetics Female Fluorescent Antibody Technique Gene Deletion Genomics Histocompatibility Antigens Class II / genetics Histone Demethylases / genetics Histone-Lysine N-Methyltransferase / genetics Humans Kidney Neoplasms / drug therapy Lymphocytes, Tumor-Infiltrating / immunology Male Middle Aged Mutation Nivolumab / therapeutic use PTEN Phosphohydrolase / genetics Prognosis Proteasome Endopeptidase Complex / genetics Sequence Analysis, RNA TOR Serine-Threonine Kinases / genetics Transcription Factors / genetics Tuberous Sclerosis Complex 1 Protein / genetics Tumor Suppressor Proteins / genetics Ubiquitin Thiolesterase / genetics Von Hippel-Lindau Tumor Suppressor Protein / genetics Exome Sequencing

Journal

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

Informations de publication

Date de publication:
06 2020
Historique:
received: 22 12 2019
accepted: 16 03 2020
pubmed: 31 5 2020
medline: 9 9 2020
entrez: 31 5 2020
Statut: ppublish

Résumé

PD-1 blockade has transformed the management of advanced clear cell renal cell carcinoma (ccRCC), but the drivers and resistors of the PD-1 response remain incompletely elucidated. Here, we analyzed 592 tumors from patients with advanced ccRCC enrolled in prospective clinical trials of treatment with PD-1 blockade by whole-exome and RNA sequencing, integrated with immunofluorescence analysis, to uncover the immunogenomic determinants of the therapeutic response. Although conventional genomic markers (such as tumor mutation burden and neoantigen load) and the degree of CD8

Identifiants

DOI: 10.1038/s41591-020-0839-y PMID: 32472114 PMC: PMC7499153
pubmed: 32472114
doi: 10.1038/s41591-020-0839-y
pii: 10.1038/s41591-020-0839-y
pmc: PMC7499153
mid: NIHMS1611472
doi:

Substances chimiques

Antineoplastic Agents, Immunological 0
BAP1 protein, human 0
DNA-Binding Proteins 0
Histocompatibility Antigens Class II 0
PBRM1 protein, human 0
TSC1 protein, human 0
Transcription Factors 0
Tuberous Sclerosis Complex 1 Protein 0
Tumor Suppressor Proteins 0
Nivolumab 31YO63LBSN
Histone Demethylases EC 1.14.11.-
KDM5C protein, human EC 1.14.11.-
Histone-Lysine N-Methyltransferase EC 2.1.1.43
SETD2 protein, human EC 2.1.1.43
Von Hippel-Lindau Tumor Suppressor Protein EC 2.3.2.27
MTOR protein, human EC 2.7.1.1
Class I Phosphatidylinositol 3-Kinases EC 2.7.1.137
PIK3CA protein, human EC 2.7.1.137
TOR Serine-Threonine Kinases EC 2.7.11.1
PTEN Phosphohydrolase EC 3.1.3.67
PTEN protein, human EC 3.1.3.67
Ubiquitin Thiolesterase EC 3.4.19.12
Proteasome Endopeptidase Complex EC 3.4.25.1
VHL protein, human EC 6.3.2.-

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

909-918

Subventions

Organisme : NCI NIH HHS
ID : P50 CA101942
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA009172
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA155010
Pays : United States
Organisme : NCI NIH HHS
ID : U24 CA224331
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA211482
Pays : United States

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Auteurs

David A Braun (DA)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0003-4543-5553

Yue Hou (Y)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA, USA.

Ziad Bakouny (Z)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0003-1906-5704

Miriam Ficial (M)

Harvard Medical School, Boston, MA, USA.
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
ORCID: 0000-0002-2005-9267

Miriam Sant' Angelo (M)

Harvard Medical School, Boston, MA, USA.
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.

Juliet Forman (J)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA, USA.

Petra Ross-Macdonald (P)

Bristol-Myers Squibb, Princeton, NJ, USA.

Ashton C Berger (AC)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Opeyemi A Jegede (OA)

Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.

Liudmilla Elagina (L)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

John Steinharter (J)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Maxine Sun (M)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.

Megan Wind-Rotolo (M)

Bristol-Myers Squibb, Princeton, NJ, USA.

Jean-Christophe Pignon (JC)

Harvard Medical School, Boston, MA, USA.
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.

Andrew D Cherniack (AD)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Lee Lichtenstein (L)

Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Donna Neuberg (D)

Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.
ORCID: 0000-0003-2566-3145

Paul Catalano (P)

Harvard Medical School, Boston, MA, USA.
Department of Data Sciences, Dana-Farber Cancer Institute, Boston, MA, USA.

Gordon J Freeman (GJ)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-7210-5616

Arlene H Sharpe (AH)

Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0002-9736-2109

David F McDermott (DF)

Harvard Medical School, Boston, MA, USA.
Medical Oncology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
ORCID: 0000-0002-2675-5095

Eliezer M Van Allen (EM)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Harvard Medical School, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
ORCID: 0000-0002-0201-4444

Sabina Signoretti (S)

Harvard Medical School, Boston, MA, USA.
Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA, USA.

Catherine J Wu (CJ)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. cwu@partners.org.
Harvard Medical School, Boston, MA, USA. cwu@partners.org.
Broad Institute of MIT and Harvard, Cambridge, MA, USA. cwu@partners.org.
ORCID: 0000-0002-3348-5054

Sachet A Shukla (SA)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. sachet_shukla@dfci.harvard.edu.
Broad Institute of MIT and Harvard, Cambridge, MA, USA. sachet_shukla@dfci.harvard.edu.
Translational Immunogenomics Lab, Dana-Farber Cancer Institute, Boston, MA, USA. sachet_shukla@dfci.harvard.edu.
ORCID: 0000-0003-2445-3584

Toni K Choueiri (TK)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA. toni_choueiri@dfci.harvard.edu.
Harvard Medical School, Boston, MA, USA. toni_choueiri@dfci.harvard.edu.
ORCID: 0000-0002-9201-3217

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Interplay of somatic alterations and immune...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Interplay of somatic alterations and immune...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Sujet âgé de 80 ans ou plus › Interplay of somatic alterations and immune...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité acquise › Immunité cellulaire › Présentation d'antigène › Interplay of somatic alterations and immune...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Antinéoplasiques immunologiques › Interplay of somatic alterations and immune...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD8+ › Interplay of somatic alterations and immune...
questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Tumeurs urologiques › Tumeurs du rein › Néphrocarcinome › Interplay of somatic alterations and immune...
questionsmedicales.fr › Phénomènes génétiques › Ploïdies › Aneuploïdie › Monosomie › Délétion de segment de chromosome › Interplay of somatic alterations and immune...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Chromosomes › Chromosomes de mammifère › Chromosomes humains › Chromosomes humains 6-12 et X › Chromosomes humains de la paire 6 › Interplay of somatic alterations and immune...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Chromosomes › Chromosomes de mammifère › Chromosomes humains › Chromosomes humains 6-12 et X › Chromosomes humains de la paire 9 › Interplay of somatic alterations and immune...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Phosphatidylinositol 3-kinases › Phosphatidylinositol-4-phosphate 3-kinase › Phosphatidylinositol 3-kinases de classe I › Interplay of somatic alterations and immune...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines de liaison à l'ADN › Interplay of somatic alterations and immune...
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Technique d'immunofluorescence › Interplay of somatic alterations and immune...
questionsmedicales.fr › Phénomènes génétiques › Mutagenèse › Délétion de séquence › Délétion de gène › Interplay of somatic alterations and immune...
questionsmedicales.fr › Disciplines des sciences naturelles › Disciplines des sciences biologiques › Biologie › Génétique › Génomique › Interplay of somatic alterations and immune...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Isoantigènes › Antigènes d'histocompatibilité › Antigènes d'histocompatibilité de classe II › Interplay of somatic alterations and immune...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Oxidoreductases › Oxidoreductases acting on CH-NH group donors › Oxidoreductases, (N-demethylating) › Histone Demethylases › Interplay of somatic alterations and immune...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Transferases › One-carbon group transferases › Methyltransferases › Protein Methyltransferases › Histone méthyltransférases › Histone-lysine N-methyltransferase › Interplay of somatic alterations and immune...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Interplay of somatic alterations and immune...
questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Tumeurs urologiques › Tumeurs du rein › Interplay of somatic alterations and immune...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes TIL › Interplay of somatic alterations and immune...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Adulte d'âge moyen › Interplay of somatic alterations and immune...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › Interplay of somatic alterations and immune...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux humanisés › Nivolumab › Interplay of somatic alterations and immune...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Phosphohydrolase PTEN › Interplay of somatic alterations and immune...
questionsmedicales.fr › Diagnostic › Pronostic › Interplay of somatic alterations and immune...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Complexes multienzymatiques › Proteasome endopeptidase complex › Interplay of somatic alterations and immune...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ARN › Interplay of somatic alterations and immune...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-Serine-Threonine Kinases › Sérine-thréonine kinases TOR › Interplay of somatic alterations and immune...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Interplay of somatic alterations and immune...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Protéine-1 du complexe de la sclérose tubéreuse › Interplay of somatic alterations and immune...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Interplay of somatic alterations and immune...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines associées à la maladie de Parkinson › Ubiquitin thiolesterase › Interplay of somatic alterations and immune...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines tumorales › Protéines suppresseurs de tumeurs › Protéine Von Hippel-Lindau supresseur de tumeur › Interplay of somatic alterations and immune...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Analyse de séquence › Analyse de séquence d'ADN › Séquençage du génome entier › Séquençage de l'exome › Interplay of somatic alterations and immune...