Metabolomic adaptations and correlates of survival to immune checkpoint blockade.

Adaptation, Physiological / drug effects Aged Antineoplastic Agents / therapeutic use Carcinoma, Renal Cell / blood Clinical Trials as Topic Everolimus / therapeutic use Female Humans Kaplan-Meier Estimate Kidney Neoplasms / blood Kynurenine / blood Male Melanoma / blood Metabolomics Middle Aged Nivolumab / therapeutic use Programmed Cell Death 1 Receptor / antagonists & inhibitors Treatment Outcome Tryptophan / blood

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
25 09 2019
Historique:
received: 24 06 2019
accepted: 29 08 2019
entrez: 27 9 2019
pubmed: 27 9 2019
medline: 14 1 2020
Statut: epublish

Résumé

Despite remarkable success of immune checkpoint inhibitors, the majority of cancer patients have yet to receive durable benefits. Here, in order to investigate the metabolic alterations in response to immune checkpoint blockade, we comprehensively profile serum metabolites in advanced melanoma and renal cell carcinoma patients treated with nivolumab, an antibody against programmed cell death protein 1 (PD1). We identify serum kynurenine/tryptophan ratio increases as an adaptive resistance mechanism associated with worse overall survival. This advocates for patient stratification and metabolic monitoring in immunotherapy clinical trials including those combining PD1 blockade with indoleamine 2,3-dioxygenase/tryptophan 2,3-dioxygenase   (IDO/TDO) inhibitors.

Identifiants

DOI: 10.1038/s41467-019-12361-9 PMID: 31554815 PMC: PMC6761178
pubmed: 31554815
doi: 10.1038/s41467-019-12361-9
pii: 10.1038/s41467-019-12361-9
pmc: PMC6761178
doi:

Substances chimiques

Antineoplastic Agents 0
PDCD1 protein, human 0
Programmed Cell Death 1 Receptor 0
Nivolumab 31YO63LBSN
Kynurenine 343-65-7
Tryptophan 8DUH1N11BX
Everolimus 9HW64Q8G6G

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

4346

Subventions

Organisme : NIDDK NIH HHS
ID : P30 DK040561
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA211482
Pays : United States

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Auteurs

Haoxin Li (H)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, 02138, USA.

Kevin Bullock (K)

Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.

Carino Gurjao (C)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.

David Braun (D)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.

Sachet A Shukla (SA)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.

Dominick Bossé (D)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
ORCID: 0000-0003-2992-5632

Aly-Khan A Lalani (AA)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
ORCID: 0000-0002-9907-9112

Shuba Gopal (S)

Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.

Chelsea Jin (C)

Bristol-Myers Squibb, Princeton, NJ, 08540, USA.

Christine Horak (C)

Bristol-Myers Squibb, Princeton, NJ, 08540, USA.

Megan Wind-Rotolo (M)

Bristol-Myers Squibb, Princeton, NJ, 08540, USA.

Sabina Signoretti (S)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.

David F McDermott (DF)

Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.

Gordon J Freeman (GJ)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
ORCID: 0000-0002-7210-5616

Eliezer M Van Allen (EM)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
ORCID: 0000-0002-0201-4444

Stuart L Schreiber (SL)

Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, 02138, USA.

F Stephen Hodi (F)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.

William R Sellers (WR)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
ORCID: 0000-0002-3539-9803

Levi A Garraway (LA)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.

Clary B Clish (CB)

Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
ORCID: 0000-0001-8259-9245

Toni K Choueiri (TK)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA. Toni_Choueiri@dfci.harvard.edu.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. Toni_Choueiri@dfci.harvard.edu.
ORCID: 0000-0002-9201-3217

Marios Giannakis (M)

Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA. Marios_Giannakis@dfci.harvard.edu.
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. Marios_Giannakis@dfci.harvard.edu.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. Marios_Giannakis@dfci.harvard.edu.

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Classifications MeSH

questionsmedicales.fr › Phénomènes biologiques › Adaptation biologique › Adaptation physiologique › Metabolomic adaptations and correlates of...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Sujet âgé › Metabolomic adaptations and correlates of...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Metabolomic adaptations and correlates of...
questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Tumeurs urologiques › Tumeurs du rein › Néphrocarcinome › Metabolomic adaptations and correlates of...
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questionsmedicales.fr › Composés chimiques organiques › Lactones › Sirolimus › Évérolimus › Metabolomic adaptations and correlates of...
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questionsmedicales.fr › Maladies urogénitales › Maladies urologiques › Tumeurs urologiques › Tumeurs du rein › Metabolomic adaptations and correlates of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Acides aminés › Cynurénine › Metabolomic adaptations and correlates of...
questionsmedicales.fr › Tumeurs › Tumeurs par type histologique › Naevus et mélanomes › Mélanome › Metabolomic adaptations and correlates of...
questionsmedicales.fr › Disciplines des sciences naturelles › Chimie › Biochimie › Métabolomique › Metabolomic adaptations and correlates of...
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