The immunosuppressive microenvironment caused by several intrinsic and extrinsic mechanism has brought great challenges to the immunotherapy of pancreatic cancer. We identified GFPT2, the key enzyme in hexosamine biosynthesis pathway (HBP), as an immune-related prognostic gene in pancreatic cancer using transcriptome sequencing and further confirmed that GFPT2 promoted macrophage M2 polarization and malignant phenotype of pancreatic cancer. HBP is a glucose metabolism pathway leading to the generation of uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), which is further utilized for protein O-GlcNAcylation. We confirmed GFPT2-mediated O-GlcNAcylation played an important role in regulating immune microenvironment. Through cellular proteomics, we identified IL-18 as a key downstream of GFPT2 in regulating the immune microenvironment. Through CO-IP and protein mass spectrum, we confirmed that YBX1 was O-GlcNAcylated and nuclear translocated by GFPT2-mediated O-GlcNAcylation. Then, YBX1 functioned as a transcription factor to promote IL-18 transcription. Our study elucidated the relationship between the metabolic pathway of HBP in cancer cells and the immune microenvironment, which might provide some insights into the combination therapy of HBP vulnerability and immunotherapy in pancreatic cancer.
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http://dx.doi.org/10.1038/s41419-024-06589-7 | DOI Listing |
Langenbecks Arch Surg
December 2024
Department of Surgery, TUM Universitätsklinikum Klinikum Rechts der Isar Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany.
Objective: Splenectomy is regularly performed in total and distal pancreatectomy due to technical reasons, lymph node dissection and radicality of the operation. However, the spleen serves as an important organ for competent immune function, and its removal is associated with an increased incidence of cancer and a worse outcome in some cancer entities (Haematologica 99:392-398, 2014; Dis Colon Rectum 51:213-217, 2008; Dis Esophagus 21:334-339, 2008). The impact of splenectomy in pancreatic cancer is not fully resolved (J Am Coll Surg 188:516-521, 1999; J Surg Oncol 119:784-793, 2019).
View Article and Find Full Text PDFJ Exp Clin Cancer Res
December 2024
The National Engineering Laboratory for Anti-Tumor Protein Therapeutics, Tsinghua University, Beijing, 100084, China.
Cell Signal
December 2024
Department of Maxillofacial and Otorhinolaryngology Oncology and Department of Head and Neck Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China; National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China; Tianjin Key Laboratory of Basic and Translational Medicine on Head & Neck Cancer, Tianjin, China; Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China. Electronic address:
Nerves are often overlooked as key components of the tumor microenvironment. However, the molecular mechanisms underlying the reciprocal interactions between tumors and nerves remain largely unknown. In this study, we analyzed data from The Cancer Genome Atlas (TCGA) and identified a significant association between DKK1 expression and poor prognosis, as well as a correlation between DKK1 expression and myeloid-derived suppressor cell (MDSC) infiltration in head and neck squamous cell carcinoma (HNSCC) and pancreatic ductal adenocarcinoma (PDAC), two cancer types characterized by pronounced tumor-nerve interactions.
View Article and Find Full Text PDFAnn Surg Oncol
December 2024
Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Background: Pancreatic enucleation is a reliable surgical method for treating benign and borderline pancreatic tumors; however, the incidence of postoperative pancreatic fistula (POPF) is high, especially when the tumor is close to the main pancreatic duct. This study aimed to reduce the incidence of pancreatic fistula by preoperative placement of pancreatic stents and to summarize our center's experience with this procedure.
Methods: From June 2020 to July 2023, patients diagnosed with benign or borderline pancreatic tumors at Renji Hospital were included.
BMC Surg
December 2024
Department of Surgery, Transplantation and Gastroenterology, Semmelweis University, Budapest, Hungary.
Background: Biliary leakage is a serious complication of hepato-pancreato-biliary operations, increasing morbidity and mortality, and challenging clinicians.
Objective: This study aims to evaluate the incidence of bilioenteric anastomotic leakage, treatment options, and their outcomes at a high-volume tertiary referral center.
Methods: A retrospective cohort study was conducted to analyze the outcomes of patients who underwent biliary anastomosis formation between 2016 and 2021.
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