{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Huang TX"],"funding":["National Natural Science Foundation of China (National Science Foundation of China)"],"pagination":["5680"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11227557"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["15(1)"],"pubmed_abstract":["Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-β1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-β1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8<su"],"journal":["Nature communications"],"pubmed_title":["ATP6V0A1-dependent cholesterol absorption in colorectal cancer cells triggers immunosuppressive signaling to inactivate memory CD8<sup>+</sup> T cells."],"pmcid":["PMC11227557"],"funding_grant_id":["82173003"],"pubmed_authors":["Zhang TT","Lu XF","Huang TX","Zou C","Xie Q","Long QY","Bi J","Huang HS","Dong SW","Huang LY","Yang Y","Pan F","Zhao P","Chen JY","Fu L","Li HH","Zhang B"],"additional_accession":[]},"is_claimable":false,"name":"ATP6V0A1-dependent cholesterol absorption in colorectal cancer cells triggers immunosuppressive signaling to inactivate memory CD8<sup>+</sup> T cells.","description":"Obesity shapes anti-tumor immunity through lipid metabolism; however, the mechanisms underlying how colorectal cancer (CRC) cells utilize lipids to suppress anti-tumor immunity remain unclear. Here, we show that tumor cell-intrinsic ATP6V0A1 drives exogenous cholesterol-induced immunosuppression in CRC. ATP6V0A1 facilitates cholesterol absorption in CRC cells through RAB guanine nucleotide exchange factor 1 (RABGEF1)-dependent endosome maturation, leading to cholesterol accumulation within the endoplasmic reticulum and elevated production of 24-hydroxycholesterol (24-OHC). ATP6V0A1-induced 24-OHC upregulates TGF-β1 by activating the liver X receptor (LXR) signaling. Subsequently, the release of TGF-β1 into the tumor microenvironment by CRC cells activates the SMAD3 pathway in memory CD8<su","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Jul","modification":"2025-04-22T15:35:44.769Z","creation":"2025-04-06T01:24:49.826Z"},"accession":"S-EPMC11227557","cross_references":{"pubmed":["38971819"],"doi":["10.1038/s41467-024-50077-7"]}}