Metabolomic adaptations and correlates of survival to immune checkpoint blockade.

Nat Commun
Authors
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.

Year of Publication
2019
Journal
Nat Commun
Volume
10
Issue
1
Pages
4346
Date Published
2019 Sep 25
ISSN
2041-1723
DOI
10.1038/s41467-019-12361-9
PubMed ID
31554815
Links
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)