Nikeghbal, ParisaBurke, DanielleArmijo, DaletAldarondo-Quiñones, SamuelLidke, Diane S.Steinkamp, Mara P.2026-03-042026-03-042025-122162-4011PMC12320822https://hdl.handle.net/10919/141662While 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). <i>In vitro</i> 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 <i>in vitro</i>, 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.application/pdfenCreative Commons Attribution-NonCommercial 4.0 InternationalChemotherapyhumanized PDXimmunotherapyorganoidsovarian cancerpatient-derived modelstumor microenvironmenttumor-associated macrophagesOrganoidsCell Line, TumorAnimalsHumansMiceOvarian NeoplasmsPaclitaxelXenograft Model Antitumor AssaysDrug Resistance, NeoplasmFemaleTumor MicroenvironmentTumor-Associated MacrophagesArticle - Refereedhttps://doi.org/10.1080/2162402x.2025.2537710141Nikeghbal, Parisa [0000-0002-6954-7544]407476802162-402X