Summary of Study ST001236

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR000828. The data can be accessed directly via it's Project DOI: 10.21228/M8NQ4J This work is supported by NIH grant, U2C- DK119886.


This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST001236
Study TitleMetabolic responses to PD1 immune-checkpoint blockade and association with therapeutic benefits - Part II
Study SummaryInhibition of immune-checkpoint targets including PD1 is clinically effective in a variety of cancers. However, only a subset of patients respond and complete response remains uncommon. Given the known role of metabolites in modulating immunity, we sought to understand how individual patients’ metabolic activities adapt to PD1 immune checkpoint blockade and how they associate with therapeutic benefits. To this end, we profiled metabolites in pre- and multiple on-treatment patient serum samples from three independent immunotherapy trials using hydrophilic interaction liquid chromatography coupled with either triple quadrupole MS multiple reaction monitoring or high resolution full scan MS detection. The study consisted of two Phase I trials (CA209-038, NCT01621490; CA209-009, NCT01358721) which included 78 patients with advanced melanoma and 91 patients with metastatic renal cell carcinoma (RCC) treated with nivolumab. To investigate the generalizability of our results, we also analyzed a large randomized Phase III trial (CheckMate 025, NCT01668784) with 743 RCC patients, among which 394 received nivolumab and 349 received everolimus. V600E is the most common BRAF mutation in melanoma and BRAF_V600E indicates the mutation status.
Broad Institute of MIT and Harvard
Last NameClish
First NameClary
Address415 Main St, Cambridge, MA 02142
Submit Date2019-08-12
Num Groups1
Total Subjects91
Num Males61
Num Females30
Raw Data AvailableYes
Raw Data File Type(s)raw(Thermo)
Analysis Type DetailLC-MS
Release Date2019-08-27
Release Version1
Clary Clish Clary Clish application/zip

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Project ID:PR000828
Project DOI:doi: 10.21228/M8NQ4J
Project Title:Metabolomic adaptations and correlates of survival to immune checkpoint blockade
Project Type:Serum metabolomcs
Project Summary:To investigate the metabolic alterations in response to immune checkpoint blockade, we comprehensively profiled serum metabolites in advanced melanoma and renal cell carcinoma patients treated with nivolumab, an antibody against programmed cell death protein 1 (PD1). We identified 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 IDO/TDO inhibitors.
Institute:Broad Institute of MIT and Harvard
Department:Metabolomics Platform
Last Name:Clish
First Name:Clary
Address:415 Main Street, Cambridge, MA, 02142, USA
Funding Source:Conquer Cancer Foundation ASCO Career Development Award; Stand Up To Cancer Colorectal Cancer Dream Team Translational Research Grant (grant number: SU2C-AACR-DT22-17); the Dana-Farber/Harvard Cancer Center Kidney Cancer program; NCI's Cancer Target Discovery and Development (CTD2) Network (grant number: U01CA217848); Kidney SPORE P50CA101942-12; the Trust Family, Michael Brigham, and Loker Pinard Funds for Kidney Cancer Research at Dana-Farber Cancer Institute; the BMS II-ON consortium; and the AACR KureIt Grant for Kidney Cancer.
Contributors:Haoxin Li, Kevin Bullock, Carino Gurjao, David Braun, Sachet Shukla, Dominick Bossé, Aly-Khan A. Lalani, Shuba Gopal, Chelsea Jin, Christine Horak, Megan Wind-Rotolo, Sabina Signoretti, David F. McDermott, Gordon J. Freeman, Eliezer M. Van Allen, Stuart L. Schreiber, F. Stephen Hodi, William R. Sellers, Levi A. Garraway, Clary Clish, Toni K. Choueiri, Marios Giannakis