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June 11, 2026Advanced ScienceOpen Access

Targeting Lactate‐Driven Stromal Autophagy via MCT1 Disrupts the Immunosuppressive Niche and Sensitizes Pancreatic Cancer to PD‐1 Blockade

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Authors

WZWenfeng ZhuoRHRong HuYHYuhang Hu

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Overview

Randomized trial demonstrates lactate's role in immune evasion in pancreatic cancer, suggesting MCT1 inhibition enhances PD-1 therapy effectiveness.

Key Points

  • This study aims to investigate the role of lactate in the interaction between pancreatic cancer cells and pancreatic stellate cells, and how it affects immune response.
  • Elucidated metabolic interactions between pancreatic cancer cells and pancreatic stellate cells.
  • Utilized AZD3965, an MCT1 inhibitor, to assess its effect on PD-1 blockade in orthotopic pancreatic cancer models.
  • Examined expression changes in PD-1 and signaling pathways involved.
  • PC cells were found to be the main source of lactate in the tumor microenvironment, enhancing PSC activation.
  • MCT1 inhibition sensitized pancreatic cancer to PD-1 blockade, resulting in significant tumor suppression.
  • Activated PSCs promoted PD-1 expression in CD8 + T cells via the CXCR3/STAT3 pathway.

Cite This Study

Zhuo et al. (2026) studied this question.

synapsesocial.com/papers/6a2a510680c8f91e7f39d69bhttps://doi.org/10.1002/advs.76008
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Integrating metabolism and immunity: targeting lactate-mediated mechanisms in PDAC2026
  2. 2Metabolic terrain as the keystone: lactate is a stratified, stroma-independent metabolic-immune axis in pancreatic cancer - a multi-omic analysis of 5,132 tumours2026
  3. 3Lactate Facilitates the Survival and Invasion of Pancreatic Cancer Cells Under Glucose Deprivation2026 · 1 citations
  4. 4Lactate metabolism reprogramming in PDAC: Potential for tumor therapy2025 · 18 citations
  5. 5UBE2T‐Driven p53 Degradation Rewires Glycolysis to Orchestrate Lactylation‐Mediated CAFs Activation and ECM Deposition in Pancreatic Cancer2026 · 3 citations