Cargando…
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...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| 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 |
| _version_ | 1783453972053360640 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Li, Haoxin |
| collection | PubMed |
| description | 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. |
| format | Online Article Text |
| id | pubmed-6761178 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2019 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-67611782019-09-27 Metabolomic adaptations and correlates of survival to immune checkpoint blockade 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 Nat Commun Article 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. Nature Publishing Group UK 2019-09-25 /pmc/articles/PMC6761178/ /pubmed/31554815 http://dx.doi.org/10.1038/s41467-019-12361-9 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| spellingShingle | Article 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 Metabolomic adaptations and correlates of survival to immune checkpoint blockade |
| title | Metabolomic adaptations and correlates of survival to immune checkpoint blockade |
| title_full | Metabolomic adaptations and correlates of survival to immune checkpoint blockade |
| title_fullStr | Metabolomic adaptations and correlates of survival to immune checkpoint blockade |
| title_full_unstemmed | Metabolomic adaptations and correlates of survival to immune checkpoint blockade |
| title_short | Metabolomic adaptations and correlates of survival to immune checkpoint blockade |
| title_sort | metabolomic adaptations and correlates of survival to immune checkpoint blockade |
| topic | Article |
| url | 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 |
| work_keys_str_mv | AT lihaoxin metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT bullockkevin metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT gurjaocarino metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT braundavid metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT shuklasacheta metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT bossedominick metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT lalanialykhana metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT gopalshuba metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT jinchelsea metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT horakchristine metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT windrotolomegan metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT signorettisabina metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT mcdermottdavidf metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT freemangordonj metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT vanalleneliezerm metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT schreiberstuartl metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT stephenhodif metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT sellerswilliamr metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT garrawaylevia metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT clishclaryb metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT choueiritonik metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade AT giannakismarios metabolomicadaptationsandcorrelatesofsurvivaltoimmunecheckpointblockade |