Summary of project PR001705
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
| 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 |
Summary of all studies in project PR001705
| Study ID | Study Title | Species | Institute | Analysis(* : Contains Untargted data) | Release Date | Version | Samples | Download(* : Contains raw data) |
|---|---|---|---|---|---|---|---|---|
| ST002740 | Non-targeted metabolomics screen comparing 13C2-acetate labeling of metabolites in CD8+ T cells and NK cells from mouse spleens. | Mus musculus | The Wistar Institute | MS | 2023-07-11 | 1 | 42 | Uploaded data (5.5G)* |
