{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Daneshmandi S"],"funding":["NHLBI NIH HHS","NCI NIH HHS"],"pagination":["229"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12804680"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(1)"],"pubmed_abstract":["The mechanisms underlying the metabolic adaptation of myeloid cells within the tumor microenvironment remain incompletely understood. Here, we identify 6-phosphogluconate dehydrogenase (6PGD), a rate-limiting enzyme in the pentose phosphate pathway (PPP), as an important regulator of monocytic-myeloid derived suppressor cell (M-MDSC) function. Our findings reveal that tumor M-MDSCs upregulate 6PGD expression via IL-6/STAT3 signaling. Blocking 6PGD, using either genetic or pharmacological approaches, impairs the immunosuppressive function of M-MDSCs and suppresses tumor growth. Mechanistically, 6PGD inhibition leads to the accumulation of its substrate, 6-phosphogluconate (6PG), within M-MDSCs, activates the JNK1-IRS1 and PI3K-AKT-pDRP1 signaling pathways, leading to mitochondrial fragmenta"],"journal":["Nature communications"],"pubmed_title":["6-Phosphogluconate dehydrogenase promotes mitochondrial fusion and immune suppression in tumor-associated monocytic suppressor cells."],"pmcid":["PMC12804680"],"funding_grant_id":["P30 CA177558","R01 CA205246","P30 CA016056","R50 CA283805","R00 HL155792"],"pubmed_authors":["McCarthy PL","Repasky EA","Singh PK","Yan Q","Katsuta E","Gharib E","Gomez EC","Fan TW","Wang J","Mohammadpour H","Daneshmandi S","Higashi RM","Choi JE","Lane AN"],"additional_accession":[]},"is_claimable":false,"name":"6-Phosphogluconate dehydrogenase promotes mitochondrial fusion and immune suppression in tumor-associated monocytic suppressor cells.","description":"The mechanisms underlying the metabolic adaptation of myeloid cells within the tumor microenvironment remain incompletely understood. Here, we identify 6-phosphogluconate dehydrogenase (6PGD), a rate-limiting enzyme in the pentose phosphate pathway (PPP), as an important regulator of monocytic-myeloid derived suppressor cell (M-MDSC) function. Our findings reveal that tumor M-MDSCs upregulate 6PGD expression via IL-6/STAT3 signaling. Blocking 6PGD, using either genetic or pharmacological approaches, impairs the immunosuppressive function of M-MDSCs and suppresses tumor growth. Mechanistically, 6PGD inhibition leads to the accumulation of its substrate, 6-phosphogluconate (6PG), within M-MDSCs, activates the JNK1-IRS1 and PI3K-AKT-pDRP1 signaling pathways, leading to mitochondrial fragmenta","dates":{"release":"2026-01-01T00:00:00Z","publication":"2026 Jan","modification":"2026-06-06T15:38:51.205Z","creation":"2026-06-02T03:09:03.655Z"},"accession":"S-EPMC12804680","cross_references":{"pubmed":["41535266"],"doi":["10.1038/s41467-025-68102-8"]}}