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Metabolomic adaptations and correlates of survival to immune checkpoint blockade

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 r...

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Detalles Bibliográficos
Autores principales: Li, Haoxin, Bullock, Kevin, Gurjao, Carino, Braun, David, Shukla, Sachet A., Bossé, Dominick, Lalani, Aly-Khan A., Gopal, Shuba, Jin, Chelsea, Horak, Christine, Wind-Rotolo, Megan, Signoretti, Sabina, McDermott, David F., Freeman, Gordon J., Van Allen, Eliezer M., Schreiber, Stuart L., Stephen Hodi, F., Sellers, William R., Garraway, Levi A., Clish, Clary B., Choueiri, Toni K., Giannakis, Marios
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761178/
https://www.ncbi.nlm.nih.gov/pubmed/31554815
http://dx.doi.org/10.1038/s41467-019-12361-9
Descripción
Sumario: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.