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Updated: Jun 25, 2025

Quantitation of Intra-peritoneal Ovarian Cancer Metastasis
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Transcriptome profiling and characterization of peritoneal metastasis ovarian cancer xenografts in humanized mice

Sung Wan Kang1,2, Ji-Young Lee1,2, Ok-Ju Kang1,2

  • 1Department of Obstetrics and Gynecology, Asan Medical Center, University of Ulsan College of Medicine, 88, Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea.

Scientific Reports
|May 24, 2024
PubMed

Insights

Developing humanized (Hu)-mouse models for ovarian cancer (OC) allows researchers to test immunotherapy drugs. These models revealed insights into why anti-PD-1 treatment may not be effective in some OC patients.

Area of Science:

  • Oncology
  • Immunology
  • Preclinical Models

Background:

  • Immunotherapy shows promise for ovarian cancer (OC) but requires effective preclinical models.
  • Existing OC models are underutilized for evaluating human immune responses to immuno-oncology (IO) drugs.
  • Humanized (Hu)-mouse models are crucial for understanding human immune interactions with IO therapies in OC.

Purpose of the Study:

  • To establish and validate OC xenograft Hu-mouse models for preclinical IO drug evaluation.
  • To investigate the efficacy of PD-1 blockade using pembrolizumab in a humanized OC model.
  • To explore potential mechanisms of resistance to anti-PD-1 therapy in ovarian cancer.

Main Methods:

  • Established OC xenograft Hu-mouse models by implanting human OC cells (SKOV-3 Luc, OVCAR-3 Luc) into CD34+ Hu-mice.
  • Monitored tumor growth using bioluminescence imaging (BLI).
  • Administered PD-1 blockade (pembrolizumab) and analyzed immune cell infiltration and gene expression in tumors and lymphoid organs.

Main Results:

  • Successfully generated OC xenograft Hu-mouse models with human immune cell infiltration (lymphocytes, myeloid cells) in tumors, lymph nodes, blood, and spleen.
  • Observed a high prevalence of tumor-infiltrating macrophages within the established models.
  • Identified alterations in HDAC class I target genes, epithelial-mesenchymal transition (EMT), and fibroblast-associated genes following pembrolizumab treatment.

Conclusions:

  • The developed OC xenograft Hu-mouse model is a valuable tool for preclinical IO drug efficacy studies.
  • This model provides insights into the mechanisms underlying unresponsiveness to anti-PD-1 therapy in ovarian cancer.
  • Further research using this model can help optimize immunotherapy strategies for ovarian cancer patients.

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