JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

BNIP3+ fibroblasts associated with hypoxia and inflammation predict prognosis and immunotherapy response in pancreatic ductal adenocarcinoma

  • 0Department of Hernia and Abdominal Wall, Peking University People's Hospital, Beijing, China.
Journal of Translational Medicine +

|

October 14, 2024

|

October 14, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Researchers identified a specific subtype of cancer-associated fibroblasts (CAFs), termed BNIP3+ Fibro, linked to poor pancreatic ductal adenocarcinoma (PDAC) prognosis and immunotherapy resistance. Targeting this subtype may improve PDAC treatment strategies.

Area Of Science

  • Oncology
  • Cancer Biology
  • Immunotherapy

Background

  • Pancreatic ductal adenocarcinoma (PDAC) presents significant treatment challenges due to its aggressive nature.
  • Cancer-associated fibroblasts (CAFs) within the tumor microenvironment critically influence PDAC progression and treatment outcomes.

Purpose Of The Study

  • To identify and characterize novel CAF-associated targets for enhancing PDAC treatment strategies.
  • To explore the role of specific fibroblast subtypes in PDAC progression and response to immunotherapy.

Main Methods

  • Single-cell sequencing and bioinformatics analyses were employed to classify PDAC fibroblasts into distinct subtypes.
  • Pseudochronological analysis was used to construct fibroblast differentiation trajectories.
  • Molecular biology techniques assessed the impact of BNIP3 on CAF-mediated hypoxia and inflammation.

Main Results

  • Six fibroblast subtypes were identified, with the BNIP3+ Fibro subtype showing terminal differentiation and increased hypoxia/inflammatory gene expression.
  • Higher proportions of BNIP3+ Fibro cells correlated with poorer PDAC patient survival and reduced immunotherapy response.
  • BNIP3 inhibition suppressed CAF-associated hypoxia and inflammation, and reduced pancreatic cancer cell migration and invasion.

Conclusions

  • The BNIP3+ Fibro subtype is associated with hypoxia, inflammation, and poor PDAC prognosis.
  • Signature genes within this subtype can predict immunotherapy response in PDAC patients.
  • Targeting BNIP3 offers a potential therapeutic strategy to improve PDAC treatment outcomes.

Keywords: