Summary of Study ST002740
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 PR001705. The data can be accessed directly via it's Project DOI: 10.21228/M89T4G This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
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.
| Study ID | ST002740 |
| Study Title | Non-targeted metabolomics screen comparing 13C2-acetate labeling of metabolites in CD8+ T cells and NK cells from mouse spleens. |
| Study Summary | Non-targeted metabolomics screen comparing 13C2-acetate labeling of metabolites in CD8+ T cells and NK cells from mouse spleens (wild type vs ACSS2 knockout C57Bl/6 mice). Metabolites were analyzed using a high-resolution, high-performance LC-MS analysis. |
| Institute | The Wistar Institute |
| Last Name | Schug |
| First Name | Zachary |
| Address | 3601 Spruce St, Philadelphia PA 19104 |
| zschug@wistar.org | |
| Phone | 215-898-3705 |
| Submit Date | 2023-06-20 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-07-11 |
| Release Version | 1 |
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Project:
| Project ID: | PR001705 |
| Project DOI: | doi: 10.21228/M89T4G |
| Project Title: | Acetate acts as a metabolic immunomodulator that potentiates anti-tumour immunity in breast cancer |
| Project Summary: | Acetate metabolism is an important metabolic pathway in many cancers and is controlled by acetyl-CoA synthetase 2 (ACSS2), an enzyme that catalyzes the conversion of acetate to acetyl-CoA. While the metabolic role of ACSS2 in cancer is well described, the consequences of blocking tumour acetate metabolism on the tumour microenvironment and anti-tumour immunity are unknown. We demonstrate that blocking ACSS2 switches cancer cells from acetate consumers to producers of acetate thereby freeing acetate for tumour-infiltrating lymphocytes to use as a fuel source. We show that acetate supplementation metabolically bolsters T-cell effector functions and proliferation. Targeting ACSS2 with CRISPR-Cas9 guides or a small molecule inhibitor promotes an anti-tumour immune response and enhances the efficacy of chemotherapy in preclinical breast cancer models. We propose a novel paradigm for targeting acetate metabolism in cancer in which inhibition of ACSS2 dually acts to impair tumour cell metabolism and potentiate anti-tumour immunity. |
| Institute: | The Wistar Institute |
| Last Name: | Schug |
| First Name: | Zachary |
| Address: | 3601 Spruce St, Philadelphia PA 19104 |
| Email: | zschug@wistar.org |
| Phone: | 215-898-3705 |
