The limited efficacy of immunotherapy in clinical trials in high‐grade serous ovarian cancer (HGSOC) may improve by implementing experimental models that are more reflective of human biology into preclinical studies. To address this, we developed and validated a humanized patient‐derived xenograft mouse model of HGSOC. Human hematopoietic stem cells and patient‐derived HGSOC cells were engrafted into immunodeficient mice. The mice were administered durvalumab (anti‐PD‐L1) and/or oleclumab (anti‐CD73) immunotherapy intraperitoneally twice a week for 5 weeks. The treatment showed good tolerability with no observed side effects, though it failed to elicit a measurable antitumor response. Leukocytes in primary tumors were analyzed immunohistochemically, and circulating T cells were characterized using spectral flow cytometry. All tumors exhibited an immune‐excluded immunophenotype. No significant inter‐group differences in disease burden, intratumoral leukocyte density, or circulating T cells were observed. In the durvalumab‐only group, tumor burden significantly positively correlated with intratumoral cytotoxic and regulatory T‐cell densities. This model reflects the immunotherapy resistance of human disease in line with clinical findings, providing a robust platform for studying tumor–immune interactions and immunosuppressive mechanisms in HGSOC. Impact statement Our results address the critical need for representative preclinical models for testing combination immunotherapy in HGSOC by providing a robust preclinical platform that can enhance the reliability of preclinical data and contribute to the improvement of the design and outcomes of future clinical trials.
Tandaric et al. (Sat,) studied this question.