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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| Published in | Nature communications Vol. 10; no. 1; pp. 4346 - 6 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
London
Nature Publishing Group UK
25.09.2019
Nature Publishing Group Nature Portfolio |
| Subjects | |
| Online Access | Get full text |
| ISSN | 2041-1723 2041-1723 |
| DOI | 10.1038/s41467-019-12361-9 |
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| 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.
Immune-checkpoint inhibition therapy has achieved success in a subset of patients. Here the authors profiled about 200 relevant metabolites in patient serum samples from three independent immunotherapy trials and found the serum kynurenine/tryptophan ratio increases to be associated with worse overall survival. |
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| AbstractList | 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. 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. 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.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. 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. Immune-checkpoint inhibition therapy has achieved success in a subset of patients. Here the authors profiled about 200 relevant metabolites in patient serum samples from three independent immunotherapy trials and found the serum kynurenine/tryptophan ratio increases to be associated with worse overall survival. Immune-checkpoint inhibition therapy has achieved success in a subset of patients. Here the authors profiled about 200 relevant metabolites in patient serum samples from three independent immunotherapy trials and found the serum kynurenine/tryptophan ratio increases to be associated with worse overall survival. |
| ArticleNumber | 4346 |
| Author | Bossé, Dominick Van Allen, Eliezer M. Clish, Clary B. Signoretti, Sabina Freeman, Gordon J. Sellers, William R. Choueiri, Toni K. Horak, Christine Giannakis, Marios Bullock, Kevin Braun, David Gurjao, Carino McDermott, David F. Gopal, Shuba Stephen Hodi, F. Garraway, Levi A. Lalani, Aly-Khan A. Li, Haoxin Jin, Chelsea Wind-Rotolo, Megan Schreiber, Stuart L. Shukla, Sachet A. |
| Author_xml | – sequence: 1 givenname: Haoxin surname: Li fullname: Li, Haoxin organization: Department of Medical Oncology, Dana-Farber Cancer Institute, Broad Institute of MIT and Harvard, Department of Chemistry and Chemical Biology, Harvard University – sequence: 2 givenname: Kevin surname: Bullock fullname: Bullock, Kevin organization: Broad Institute of MIT and Harvard – sequence: 3 givenname: Carino surname: Gurjao fullname: Gurjao, Carino organization: Department of Medical Oncology, Dana-Farber Cancer Institute, Broad Institute of MIT and Harvard – sequence: 4 givenname: David surname: Braun fullname: Braun, David organization: Department of Medical Oncology, Dana-Farber Cancer Institute – sequence: 5 givenname: Sachet A. surname: Shukla fullname: Shukla, Sachet A. organization: Department of Medical Oncology, Dana-Farber Cancer Institute – sequence: 6 givenname: Dominick orcidid: 0000-0003-2992-5632 surname: Bossé fullname: Bossé, Dominick organization: Department of Medical Oncology, Dana-Farber Cancer Institute – sequence: 7 givenname: Aly-Khan A. orcidid: 0000-0002-9907-9112 surname: Lalani fullname: Lalani, Aly-Khan A. organization: Department of Medical Oncology, Dana-Farber Cancer Institute – sequence: 8 givenname: Shuba surname: Gopal fullname: Gopal, Shuba organization: Broad Institute of MIT and Harvard – sequence: 9 givenname: Chelsea surname: Jin fullname: Jin, Chelsea organization: Bristol-Myers Squibb – sequence: 10 givenname: Christine surname: Horak fullname: Horak, Christine organization: Bristol-Myers Squibb – sequence: 11 givenname: Megan surname: Wind-Rotolo fullname: Wind-Rotolo, Megan organization: Bristol-Myers Squibb – sequence: 12 givenname: Sabina surname: Signoretti fullname: Signoretti, Sabina organization: Department of Medical Oncology, Dana-Farber Cancer Institute – sequence: 13 givenname: David F. surname: McDermott fullname: McDermott, David F. organization: Beth Israel Deaconess Medical Center – sequence: 14 givenname: Gordon J. orcidid: 0000-0002-7210-5616 surname: Freeman fullname: Freeman, Gordon J. organization: Department of Medical Oncology, Dana-Farber Cancer Institute – sequence: 15 givenname: Eliezer M. orcidid: 0000-0002-0201-4444 surname: Van Allen fullname: Van Allen, Eliezer M. organization: Department of Medical Oncology, Dana-Farber Cancer Institute, Broad Institute of MIT and Harvard, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School – sequence: 16 givenname: Stuart L. surname: Schreiber fullname: Schreiber, Stuart L. organization: Broad Institute of MIT and Harvard, Department of Chemistry and Chemical Biology, Harvard University – sequence: 17 givenname: F. surname: Stephen Hodi fullname: Stephen Hodi, F. organization: Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School – sequence: 18 givenname: William R. orcidid: 0000-0002-3539-9803 surname: Sellers fullname: Sellers, William R. organization: Department of Medical Oncology, Dana-Farber Cancer Institute, Broad Institute of MIT and Harvard – sequence: 19 givenname: Levi A. surname: Garraway fullname: Garraway, Levi A. organization: Department of Medical Oncology, Dana-Farber Cancer Institute, Broad Institute of MIT and Harvard, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School – sequence: 20 givenname: Clary B. orcidid: 0000-0001-8259-9245 surname: Clish fullname: Clish, Clary B. organization: Broad Institute of MIT and Harvard – sequence: 21 givenname: Toni K. orcidid: 0000-0002-9201-3217 surname: Choueiri fullname: Choueiri, Toni K. email: Toni_Choueiri@dfci.harvard.edu organization: Department of Medical Oncology, Dana-Farber Cancer Institute, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School – sequence: 22 givenname: Marios surname: Giannakis fullname: Giannakis, Marios email: Marios_Giannakis@dfci.harvard.edu organization: Department of Medical Oncology, Dana-Farber Cancer Institute, Broad Institute of MIT and Harvard, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31554815$$D View this record in MEDLINE/PubMed |
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| License | 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/. |
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| Snippet | Despite remarkable success of immune checkpoint inhibitors, the majority of cancer patients have yet to receive durable benefits. Here, in order to investigate... Immune-checkpoint inhibition therapy has achieved success in a subset of patients. Here the authors profiled about 200 relevant metabolites in patient serum... |
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| Title | Metabolomic adaptations and correlates of survival to immune checkpoint blockade |
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