迫切需要改进的前列腺癌（PCa）模型。小鼠前列腺不会自发形成肿瘤，并且在解剖学和发育上与人类前列腺不同。工程小鼠模型缺乏人类癌症的异质性，并且很少建立转移性生长。人类异种移植是一种替代方案，但依赖于免疫功能低下的宿主。因此，我们生成了具有完整人类免疫系统的 PCa 鼠异种移植模型（huNOG 和 huNOG-EXL 小鼠），以测试人性化肿瘤免疫相互作用是否会改善转移性 PCa 的建模以及激素和免疫疗法的影响。这些小鼠维持多种人类细胞谱系，包括功能性人类 T 细胞和骨髓细胞。在 22Rv1 异种移植物中，皮下肿瘤大小在不同条件下没有显着改变；然而，去势后的 huNOG 与接受恩杂鲁胺 (enza) 治疗的背景匹配的免疫功能低下小鼠的次要部位转移有所不同。在 huNOG 小鼠中，使用 enza 和抗程序性死亡 1 治疗后，VCaP 异种移植肿瘤的生长有所减少，而在 NOG 小鼠中则没有观察到治疗效果。 huNOG 和 NOG 小鼠中的 Enza 反应是不同的，并且与 enza 治疗的 huNOG 小鼠肿瘤内 T 细胞的增加以及 T 细胞活化的增加有关。在支持人类骨髓发育的 huNOG-EXL 小鼠中，存在大量免疫抑制调节 T 细胞和骨髓衍生抑制细胞 (MDSC)，并且 enza 治疗在转移方面没有显示差异。结果表明，据我们所知，第一个人类前列腺癌模型能够转移到临床相关部位，具有完整的人体免疫系统，对标准护理激素疗法有适当的反应，并且可以模拟免疫抑制和检查点抑制反应性免疫微环境。

There is tremendous need for improved prostate cancer (PCa) models. The mouse prostate does not spontaneously form tumors and is anatomically and developmentally different from the human prostate. Engineered mouse models lack the heterogeneity of human cancer and rarely establish metastatic growth. Human xenografts represent an alternative but rely on an immunocompromised host. Accordingly, we generated PCa murine xenograft models with an intact human immune system (huNOG and huNOG-EXL mice) to test whether humanizing tumor-immune interactions would improve modeling of metastatic PCa and the impact of hormonal and immunotherapies. These mice maintain multiple human cell lineages, including functional human T-cells and myeloid cells. In 22Rv1 xenografts, subcutaneous tumor size was not significantly altered across conditions; however, metastasis to secondary sites differed in castrate huNOG vs background-matched immunocompromised mice treated with enzalutamide (enza). VCaP xenograft tumors showed decreases in growth with enza and anti-Programed-Death-1 treatments in huNOG mice, and no effect was seen with treatment in NOG mice. Enza responses in huNOG and NOG mice were distinct and associated with increased T-cells within tumors of enza treated huNOG mice, and increased T-cell activation. In huNOG-EXL mice, which support human myeloid development, there was a strong population of immunosuppressive regulatory T-cells and Myeloid-Derived-Suppressor-Cells (MDSCs), and enza treatment showed no difference in metastasis. Results illustrate, to our knowledge, the first model of human PCa that metastasizes to clinically relevant locations, has an intact human immune system, responds appropriately to standard-of-care hormonal therapies, and can model both an immunosuppressive and checkpoint-inhibition responsive immune microenvironment.