Metabolomic adaptations and correlates of survival to immune checkpoint blockade

Haoxin Li, Kevin Bullock, Carino Gurjao, David Braun, Sachet A. Shukla, Dominick Bossé, Aly-Khan A. Lalani, Shuba Gopal, Chelsea Jin, Christine Horak, Megan Wind-Rotolo, Sabina Signoretti, David F. McDermott, Gordon J. Freeman, Eliezer M. Allen, Stuart L. Schreiber, F. Stephen Hodi, William R. Sellers, Levi A. Garraway, Clary B. Clish, Toni K. Choueiri () and Marios Giannakis ()
Additional contact information
Haoxin Li: Dana-Farber Cancer Institute
Kevin Bullock: Broad Institute of MIT and Harvard
Carino Gurjao: Dana-Farber Cancer Institute
David Braun: Dana-Farber Cancer Institute
Sachet A. Shukla: Dana-Farber Cancer Institute
Dominick Bossé: Dana-Farber Cancer Institute
Aly-Khan A. Lalani: Dana-Farber Cancer Institute
Shuba Gopal: Broad Institute of MIT and Harvard
Chelsea Jin: Bristol-Myers Squibb
Christine Horak: Bristol-Myers Squibb
Megan Wind-Rotolo: Bristol-Myers Squibb
Sabina Signoretti: Dana-Farber Cancer Institute
David F. McDermott: Beth Israel Deaconess Medical Center
Gordon J. Freeman: Dana-Farber Cancer Institute
Eliezer M. Allen: Dana-Farber Cancer Institute
Stuart L. Schreiber: Broad Institute of MIT and Harvard
F. Stephen Hodi: Dana-Farber Cancer Institute
William R. Sellers: Dana-Farber Cancer Institute
Levi A. Garraway: Dana-Farber Cancer Institute
Clary B. Clish: Broad Institute of MIT and Harvard
Toni K. Choueiri: Dana-Farber Cancer Institute
Marios Giannakis: Dana-Farber Cancer Institute

Nature Communications, 2019, vol. 10, issue 1, 1-6

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-12361-9

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