尽管免疫疗法在卵巢癌（OC）方面尚未取得成功，但它仍然是一种潜在的治疗策略。 OC 的临床前模型对于评估针对人体免疫成分的免疫肿瘤 (IO) 药物的功效是必要的，但尚未得到充分利用。开发具有人源化 (Hu) 免疫系统的小鼠模型可以帮助了解人类对 IO 药物的免疫反应，而这些药物在 OC 患者中已被证明效果有限。我们通过将表达荧光素酶的 SKOV-3 Luc 和 OVCAR-3 Luc OC 细胞腹腔注射到 CD34 Hu 小鼠中，建立了 OC 异种移植 Hu 小鼠模型。通过生物发光成像（BLI）监测肿瘤生长。在 SKOV-3 Luc Hu 小鼠模型中，我们评估了派姆单抗 (pembrolizumab) 阻断 PD-1 的功效。我们在这些模型中观察到肿瘤、淋巴结、血液和脾脏中存在人类淋巴细胞和骨髓细胞亚群。值得注意的是，这些肿瘤表现出肿瘤浸润巨噬细胞的高患病率。此外，我们还鉴定了用派姆单抗治疗的 Hu 小鼠肿瘤中的 HDAC I 类靶基因以及与上皮间质转化 (EMT) 和成纤维细胞相关的基因。我们的 OC 异种移植 Hu 小鼠模型为研究 IO 药物的功效提供了有价值的工具。从该模型中获得的见解为探索 OC 中抗 PD-1 治疗无反应相关的潜在机制提供了有用的信息。© 2024。作者。

Although immunotherapy has not yet been as successful in ovarian cancer (OC), it remains a potential therapeutic strategy. Preclinical models of OC are necessary to evaluate the efficacy of immuno-oncology (IO) drugs targeting human immune components but have been underutilized. Developing mouse models with a humanized (Hu) immune system can help understand the human immune response to IO drugs which have demonstrated limited effectiveness in OC patients. We established OC xenograft Hu-mouse models by intraperitoneally injecting luciferase-expressing SKOV-3 Luc and OVCAR-3 Luc OC cells into CD34+ Hu-mice. Tumor growth was monitored through bioluminescence imaging (BLI). In the SKOV-3 Luc Hu-mouse model, we assessed the efficacy of PD-1 blockade with pembrolizumab. We observed the presence of human lymphocyte and myeloid cell subsets within the tumors, lymph nodes, blood, and spleens in these models. Notably, these tumors exhibited a high prevalence of tumor-infiltrating macrophages. Furthermore, we identified HDAC class I target genes, and genes associated with epithelial-mesenchymal transition (EMT) and fibroblasts in the tumors of Hu-mice treated with pembrolizumab. Our xenograft Hu-mouse model of OC provides a valuable tool for investigating the efficacy of IO drugs. The insights gained from this model offer useful information to explore potential mechanisms associated with unresponsive anti-PD-1 treatment in OC.© 2024. The Author(s).