NSUN6 deficiency drives immune suppression in pancreatic cancer via the KDM5A-CCL2-macrophage axis

Background RNA 5-methylcytosine (m 5 C) has emerged as a critical epigenetic regulator in cancer biology, yet its role in the tumour immune microenvironment (TME) remains incompletely understood. Objective We aimed to elucidate the functional role and underlying mechanism of NOP2/Sun RNA methyltransferase 6 (NSUN6), an m 5 C methyltransferase, in shaping the TME of pancreatic ductal adenocarcinoma (PDAC). Design The clinical significance of NSUN6 was assessed in human PDAC cohorts. The impact of NSUN6 on antitumour immunity was evaluated using murine PDAC models. Single-cell RNA sequencing was employed to characterise the TME landscape of PDAC. RNA bisulfite sequencing and RNA sequencing were used to identify…

• NN
  National Natural Science Foundation of China

  Awards: 82303882, 82272694
• CP
  China Postdoctoral Science Foundation

  Award: 2023M734042
• NS
  Natural Science Foundation of Guangdong Province

  Award: 2025A1515012505