恶性胸膜间皮瘤（MPM）仍然是一种无法治愈的疾病。部分原因是缺乏能够充分概括 MPM 复杂性和异质性的实验模型，这是该疾病治疗管理的主要挑战。此外，MPM 微环境的贡献与治疗的适应性反应相关。我们从 MPM 胸腔积液中建立了间皮瘤患者来源的类器官 (mPDO) 培养物，并测试了它们对培美曲塞和顺铂的反应。我们的目的是评估间皮瘤相关成纤维细胞 (MAF) 对培美曲塞和顺铂 (PC) 反应的贡献。使用特定的生长培养基和条件来扩增胸腔积液衍生细胞，从八名 MPM 患者身上获得类器官培养物。使用流式细胞术验证类器官培养物与原始样品的相似性。分离 MAF 并与 mPDO 共培养，添加 MAF 降低了 mPDO 对 PC 的敏感性。经处理的 MAF 的条件培养基改变了类器官的形成和癌症干细胞标记物（如 ABCG2、NANOG 和 CD44）的表达。我们确定 IL-6 是化疗反应减弱的主要因素。 MAF 分泌的 IL-6 与 mPDO 对培美曲塞和顺铂的耐药性增加相关。

Malignant pleural mesothelioma (MPM) remains an incurable disease. This is partly due to the lack of experimental models that fully recapitulate the complexity and heterogeneity of MPM, a major challenge for therapeutic management of the disease. In addition, the contribution of the MPM microenvironment is relevant for the adaptive response to therapy. We established mesothelioma patient-derived organoid (mPDO) cultures from MPM pleural effusions and tested their response to pemetrexed and cisplatin. We aimed to evaluate the contribution of mesothelioma-associated fibroblasts (MAFs) to the response to pemetrexed and cisplatin (P+C). Organoid cultures were obtained from eight MPM patients using specific growth media and conditions to expand pleural effusion-derived cells. Flow cytometry was used to verify the similarity of the organoid cultures to the original samples. MAFs were isolated and co-cultured with mPDOs, and the addition of MAFs reduced the sensitivity of mPDOs to P+C. Organoid formation and expression of cancer stem cell markers such as ABCG2, NANOG, and CD44 were altered by conditioned media from treated MAFs. We identified IL-6 as the major contributor to the attenuated response to chemotherapy. IL-6 secretion by MAFs is correlated with increased resistance of mPDOs to pemetrexed and cisplatin.