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An Orthotopic Model of Serous Ovarian Cancer in Immunocompetent Mice for in vivo Tumor Imaging and Monitoring of Tumor Immune Responses
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TGF-β-driven T-cell exclusion in ovarian cancer: single-cell and spatial transcriptomic views of immune low-response

Jiang He1, Jun Tao2, Yu Zhou2

  • 1Yibin Institute of Traditional Chinese Medicine, Yibin, Sichuan, China.

Frontiers in Immunology
|November 3, 2025
PubMed

Insights

Transforming ovarian cancer treatment involves overcoming TGF-β-driven barriers. New strategies integrate TGF-β insights with immunotherapy to improve patient outcomes in epithelial ovarian cancer.

Area of Science:

  • Oncology and Immunology
  • Molecular Biology and Genetics
  • Cancer Research

Background:

  • Epithelial ovarian cancer (EOC) is a highly lethal malignancy with limited durable responses to current immunotherapies.
  • Tumor microenvironment, particularly transforming growth factor-beta (TGF-β)-mediated stromal barriers and T-cell exclusion, restricts immunotherapy efficacy.
  • Single-cell profiling technologies offer unprecedented resolution of cellular interactions within the tumor microenvironment.

Purpose of the Study:

  • To review advances in understanding TGF-β signaling in EOC.
  • To identify translational opportunities for precision immuno-oncology by modulating TGF-β pathways.
  • To discuss challenges and outline pragmatic standards for clinical implementation of novel strategies.

Main Methods:

  • Integration of single-cell RNA sequencing (scRNA-seq) and ATAC sequencing (scATAC-seq) to profile cellular programs.
  • Application of spatial transcriptomics to map cellular interactions and spatial biomarkers.
  • Review and synthesis of current literature on TGF-β signaling, immuno-oncology, and therapeutic strategies in EOC.

Main Results:

  • TGF-β signaling influences fibroblast, tumor, and immune cell programs, contributing to stromal barriers and T-cell exclusion.
  • Specific TGF-β-informed readouts (e.g., INHBA+ CAFs, periostin, fibronectin, MHC-I status, CD8-tumor distance) are identified.
  • Emerging strategies aim to combine TGF-β pathway modulation with checkpoint inhibitors to enhance anti-tumor immunity.

Conclusions:

  • Modulating TGF-β signaling holds significant promise for enhancing immunotherapy efficacy in epithelial ovarian cancer.
  • Integrating TGF-β-informed biomarkers and pathway inhibitors with PD-1-based regimens can overcome treatment resistance.
  • Addressing heterogeneity and standardizing assays are crucial for successful clinical translation of precision immuno-oncology approaches.
Keywords:
T-cell exclusionTGF-β signallingovarian cancersingle-cell RNA/ATACspatial transcriptomics

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