Summary of project PR002657
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR002657. The data can be accessed directly via it's Project DOI: 10.21228/M86P0N This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Project ID: | PR002657 |
| Project DOI: | doi: 10.21228/M86P0N |
| Project Title: | Intra-tumoral hypoxia promotes CD8+ T cell dysfunction via chronic activation of integrated stress response transcription factor ATF4 |
| Project Summary: | This study investigates TME metabolic alterations in T cells caused by chronic expression of ATF4 in the context of antitumor immunity. T cells were isolated, extracted in 80% methanol, and subjected to untargeted metabolomic profiling by high-resolution LC–MS/MS. To test the role of chronic ATF4 in T cells we used four biological replicates were analyzed per group, including OT-1-ATF4Tg/Tg and OT-1-E8IcreATF4Tg/Tg. Samples were processed to quantify hydrophilic metabolites, normalized to protein content and total ion counts, and analyzed using statistical and pathway enrichment approaches. The resulting dataset provides a comprehensive profile of metabolic changes in tumor antigen–specific T cells and will support mechanistic studies on how transcriptional regulation and the tumor microenvironment influence T cell metabolism. Chronic ATF4 signaling led to robust increases in tricarboxylic acid (TCA) cycle intermediates and enforced unrestrained electron transport chain (ETC) activity, as indicated by reduced succinate:α-KG, fumarate:α-KG, and 2-HG:α-KG ratios. However, unchanged NADH:NAD ratios revealed a failure of complex I to keep pace with accelerated TCA metabolism. These findings demonstrate that sustained ATF4 activity promotes hyperactive mitochondrial metabolism, driving T cell exhaustion, mitochondrial defects, and apoptosis. |
| Institute: | University of North Carolina at Chapel Hill |
| Department: | Pharmacology |
| Laboratory: | Thaxton Lab |
| Last Name: | Alicea Pauneto |
| First Name: | Coral del Mar |
| Address: | 5229 Marsico Hall, University of North Carolina at Chapel Hill, Chapel Hill, NC |
| Email: | coraldm@ad.unc.edu |
| Phone: | (919) 966-9562 |
| Publications: | Immunity Cell Press |
| Contributors: | Coral del MarAlicea Pauneto, Brian P.Riesenberg, Evelyn J.Gandy, Andrew S.Kennedy, Genevieve T.Clutton, Jessica W.Hem, Katie E.Hurst, Elizabeth G.Hunt, Jarred M.Green, Brian C.Miller, Steven P. Angus, Gary L. Johnson, Robert J.Esther, Jennifer L. Guerriero,Peng Gao, David R.Soto-Pantoja, Robert L.Ferris, Jennifer L. Modliszewski,Michael F. Coleman, H Kay Chung, Justin Milner, Stergios J. Moschos,Luke Wiseman,Jessica E.Thaxton |
Summary of all studies in project PR002657
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST004215 | Intra-tumoral hypoxia promotes CD8+ T cell dysfunction via chronic activation of integrated stress response transcription factor ATF4 | Mus musculus | University of North Carolina at Chapel Hill | MS | 2025-09-25 | 1 | 8 | Uploaded data (721.6M)* |
