Metabolomic adaptations and correlates of survival to immune checkpoint blockade.
Where this comes from
- Record sourced from PubMed, PMID 31554815.
- Also identified by DOI 10.1038/s41467-019-12361-9 and PMC identifier 6761178.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Carcinoma, Renal Cell
- Everolimus
- Kidney Neoplasms
- Melanoma
- Metabolomics
- Nivolumab