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Nat Commun. 2019 Sep 25;10(1):4346. doi: 10.1038/s41467-019-12361-9.

Metabolomic adaptations and correlates of survival to immune checkpoint blockade.

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
2
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA.
3
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, 02138, USA.
4
Bristol-Myers Squibb, Princeton, NJ, 08540, USA.
5
Beth Israel Deaconess Medical Center, Boston, MA, 02215, USA.
6
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
7
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA. Toni_Choueiri@dfci.harvard.edu.
8
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. Toni_Choueiri@dfci.harvard.edu.
9
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA. Marios_Giannakis@dfci.harvard.edu.
10
Broad Institute of MIT and Harvard, Cambridge, MA, 02142, USA. Marios_Giannakis@dfci.harvard.edu.
11
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. Marios_Giannakis@dfci.harvard.edu.

Abstract

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.

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