Summary of project PR001705

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 PR001705. The data can be accessed directly via it's Project DOI: 10.21228/M89T4G This work is supported by NIH grant, U2C- DK119886.


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

Summary of all studies in project PR001705

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : 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)*