Patient-Derived Ovarian Cancer Models Demonstrate the Influence of Tumor-Associated Macrophages on Therapeutic Response

Authors

• Parisa Nikeghbal, Department of Pathology, University of New Mexico Health Science Center, Albuquerque, NM, USA.
• Danielle Burke, Department of Pathology, University of New Mexico Health Science Center, Albuquerque, NM, USA.
• Dalet Armijo, Department of Pathology, University of New Mexico Health Science Center, Albuquerque, NM, USA.
• Samuel Aldarondo-Quiñones, Department of Pathology, University of New Mexico Health Science Center, Albuquerque, NM, USA.
• Diane S. Lidke, Department of Pathology, University of New Mexico Health Science Center, Albuquerque, NM, USA.
• Mara P. Steinkamp, Department of Pathology, University of New Mexico Health Science Center, Albuquerque, NM, USA.

Document Type

Article

Publication Date

12-1-2025

Abstract

While most ovarian cancer (OC) patients respond to front-line platinum/taxane chemotherapy and surgical debulking, the majority will develop platinum-resistance and recur. Our study investigated how tumor-associated macrophages (TAMs) within the tumor microenvironment (TME) affect chemotherapy outcomes using OC patient-derived organoids and humanized patient-derived xenografts (huPDX). In vitro macrophage migration assays demonstrated the selective recruitment of M2 macrophages to organoids. M2 macrophages, but not M1, increase organoid viability and reduce their sensitivity to paclitaxel in co-culture assays. Furthermore, BMS777607, a receptor tyrosine kinase inhibitor capable of repolarizing M2 macrophages in vitro, reduced organoid viability via a macrophage-dependent mechanism. In a platinum-sensitive huPDX model, the presence of human immune cells increased between-mouse variability in response to paclitaxel with two of four mice demonstrating tumor regrowth after two weeks. A TAM-targeted CSF-1 R inhibitor, BLZ945, combined with paclitaxel reduced tumor burden with no regrowth, suggesting that TAMs promote paclitaxel resistance in this model. Our study demonstrates that TAMs influence response to paclitaxel in both patient-derived OC organoids and huPDX. These models are useful for evaluating immunomodulatory therapy effects and could serve as a robust platform for preclinical testing of novel anti-cancer treatments, providing insights into the complex interplay between immune cells and cancer therapeutics.

Recommended Citation

Nikeghbal P, Burke D, Armijo D, Aldarondo-Quiñones S, Lidke DS, Steinkamp MP. Patient-derived ovarian cancer models demonstrate the influence of tumor-associated macrophages on therapeutic response. Oncoimmunology. 2025 Dec;14(1):2537710. doi: 10.1080/2162402X.2025.2537710. Epub 2025 Aug 1. PMID: 40747680; PMCID: PMC12320822.