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.

Details

Title
Metabolomic adaptations and correlates of survival to immune checkpoint blockade
Author
Li, Haoxin 1 ; Bullock, Kevin 2 ; Carino Gurjao 3 ; Braun, David 4 ; Shukla, Sachet A 4 ; Bossé, Dominick 4   VIAFID ORCID Logo  ; Lalani, Aly-Khan A 4   VIAFID ORCID Logo  ; Gopal, Shuba 2 ; Jin, Chelsea 5 ; Horak, Christine 5 ; Wind-Rotolo, Megan 5 ; Signoretti, Sabina 4 ; McDermott, David F 6 ; Freeman, Gordon J 4   VIAFID ORCID Logo  ; Van Allen, Eliezer M 7   VIAFID ORCID Logo  ; Schreiber, Stuart L 8 ; Hodi, F Stephen 9 ; Sellers, William R 3   VIAFID ORCID Logo  ; Garraway, Levi A 7 ; Clish, Clary B 2   VIAFID ORCID Logo  ; Choueiri, Toni K 9   VIAFID ORCID Logo  ; Giannakis, Marios 7 

 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA 
 Broad Institute of MIT and Harvard, Cambridge, MA, USA 
 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA 
 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA 
 Bristol-Myers Squibb, Princeton, NJ, USA 
 Beth Israel Deaconess Medical Center, Boston, MA, USA 
 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA 
 Broad Institute of MIT and Harvard, Cambridge, MA, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA, USA 
 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA 
Pages
1-6
Publication year
2019
Publication date
Sep 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2297119097
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.