Metabolomic adaptations and correlates of survival to immune checkpoint blockade.

Schematic of study design and serum specimen collection.

Li et al. (2019) Nat Commun. CC BY 4.0

Li H, Bullock K, Gurjao C, Braun D, Shukla SA, Bossé D, Lalani AA, Gopal S, Jin C, Horak C, Wind-Rotolo M, Signoretti S, McDermott DF, Freeman GJ, Van Allen EM, Schreiber SL, Stephen Hodi F, Sellers WR, Garraway LA, Clish CB, Choueiri TK, Giannakis M.

Nature Communications

September 25, 2019

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.

Last updated: September 27, 2019