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Nat Commun DOI:10.1038/s41467-019-12361-9

Metabolomic adaptations and correlates of survival to immune checkpoint blockade.

Publication TypeJournal Article
Year of Publication2019
AuthorsLi, H, Bullock, K, Gurjao, C, Braun, D, Shukla, SA, Bossé, D, Lalani, A-KA, Gopal, S, Jin, C, Horak, C, Wind-Rotolo, M, Signoretti, S, McDermott, DF, Freeman, GJ, Van Allen, EM, Schreiber, SL, F Hodi, S, Sellers, WR, Garraway, LA, Clish, CB, Choueiri, TK, Giannakis, M
JournalNat Commun
Date Published2019 Sep 25

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.


Alternate JournalNat Commun
PubMed ID31554815
Grant ListSU2C-AACR-DT22-17 / / EIF | Stand Up To Cancer (SU2C) /
U01CA217848 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /