|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Li, 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|
|Date Published||2019 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 Journal||Nat Commun|
|Grant List||SU2C-AACR-DT22-17 / / EIF | Stand Up To Cancer (SU2C) / |
U01CA217848 / / U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) /