articleJournal of Clinical InvestigationJan 30, 2025GOLD OA

Elevated protein lactylation promotes immunosuppressive microenvironment and therapeutic resistance in pancreatic ductal adenocarcinoma

KSKang SunXZXiaozhen ZhangJSJiatao ShiJHJinyan HuangSWSicheng Wang

Pancreas Centre (Canada) · Zhejiang University · +1 more institution

PubMed
Indexed incrossrefdoajpubmed

Abstract

Metabolic reprogramming shapes the tumor microenvironment (TME) and may lead to immunotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Elucidating the impact of pancreatic cancer cell metabolism in the TME is essential to therapeutic interventions. "Immune cold" PDAC is characterized by elevated lactate levels resulting from tumor cell metabolism, abundance of protumor macrophages, and reduced cytotoxic T cells in the TME. Analysis of fluorine-18 fluorodeoxyglucose (18F-FDG) uptake in patients showed that increased global protein lactylation in PDAC correlates with worse clinical outcomes in immunotherapy. Inhibition of lactate production in pancreatic tumors via glycolysis or mutant-KRAS…

Citation impact

73
total citations
FWCI
57.32
Percentile
100%
References
70
Citations per year

Authors

32

Topics & keywords

Topics
Keywords
  • Pancreatic ductal adenocarcinoma
  • Cancer research
  • Tumor microenvironment
  • Adenocarcinoma
  • Medicine
  • Biology
  • Pancreatic cancer
  • Internal medicine
UN Sustainable Development Goals
  • Zero hunger
No related works found for this paper.

Funding