Department of Experimental Oncology at the IEO, European Institute of Oncology IRCCS, Milan, Italy.
Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
PLoS One. 2019 Sep 19;14(9):e0217345. doi: 10.1371/journal.pone.0217345. eCollection 2019.
Since their appearance, humanized mice carrying human immune system seemed promising tools to study the crosstalk between cancer and immunity. The NOD-scidIL2Rgammanull (NSG) mice engrafted with human cord blood (hCB)-CD34+ cells have been proposed to be a valuable tool to reproduce human immune system in mouse. However, the lack of solid evidences on the functionality of their human immune components limits their usage in immune-oncology. We report that (hCB)-CD34+ cells lose their ability to propagate and originate bone marrow-derived human immune cells after two serial transplantations in NSG mice. We demonstrate that transplants of bone marrow patient-derived acute myeloid leukemias (hAMLs) grow very similarly in the humanized (hCB)-CD34+ NSG and parental NSG mice. The similar extent of engraftment and development of leukemias in (hCB)-CD34+ NSG and controls suggests a poor human immune response against not compatible hAMLs. Our findings suggest that (hCB)-CD34+ NSG mice are transient and/or incomplete carriers of the human immune system and, therefore, represent a suboptimal tool to study the interaction between tumor and immune cells.
自问世以来，携带人类免疫系统的人源化小鼠似乎是研究癌症与免疫之间相互作用的有前途的工具。带有人类脐血 (hCB)-CD34+细胞的 NOD-scidIL2Rgammanull (NSG) 小鼠被提议成为在小鼠中重现人类免疫系统的有价值工具。然而，其人类免疫成分功能缺乏确凿证据限制了它们在免疫肿瘤学中的应用。我们报告说，(hCB)-CD34+细胞在 NSG 小鼠中进行两次连续移植后，丧失了增殖和起源骨髓源性人类免疫细胞的能力。我们证明，骨髓患者来源的急性髓系白血病 (hAML) 的移植在人源化 (hCB)-CD34+ NSG 和亲本 NSG 小鼠中生长非常相似。(hCB)-CD34+ NSG 和对照中白血病的相似程度表明对不兼容的 hAML 缺乏有效的人类免疫反应。我们的研究结果表明，(hCB)-CD34+ NSG 小鼠是人类免疫系统的短暂和/或不完全载体，因此，代表了研究肿瘤与免疫细胞相互作用的次优工具。
