Bruss Christina, Kellner Kerstin, Ortmann Olaf, Seitz Stephan, Brockhoff Gero, Hutchinson James A, Wege Anja Kathrin
Department of Gynecology and Obstetrics, University Medical Center Regensburg, 93053 Regensburg, Germany.
Department of Surgery, University Hospital Regensburg, 93053 Regensburg, Germany.
Cancers (Basel). 2022 Apr 28;14(9):2214. doi: 10.3390/cancers14092214.
"Humanized" mice have been widely used for the characterization of human cancer progression and as a powerful preclinical model. Standardization of multicolor phenotyping could help to identify immune cell patterns involved in checkpoint-related complications. Therefore, we applied established protocols for immune cell profiling to our humanized Patient-Derived Xenograft (hPDX) model. hPDX are characterized by the co-existence of a human immune system and a patient-derived tumor transplant. These mice possess a human-like immune system after CD34 stem cell transplantation while the reconstitution level of the immune system was not related to the quantity of transplanted CD34 cells. Contamination ≤ 1.2% by CD3 cells in the hematopoietic stem cell (HSC) transplant did not trigger abnormal T cell maturation. Different B and T cell differentiation stages were identified, as well as regulatory T cells (Tregs) and exhausted T cells that expressed TIGIT, PD-1, or KLRG1. Overall, the application of standardized protocols for the characterization of immune cells using flow cytometry will contribute to a better understanding of immune-oncologic processes.
“人源化”小鼠已被广泛用于表征人类癌症进展，并作为一种强大的临床前模型。多色表型分析的标准化有助于识别与检查点相关并发症有关的免疫细胞模式。因此，我们将既定的免疫细胞分析方案应用于我们的人源化患者来源异种移植（hPDX）模型。hPDX的特点是人类免疫系统和患者来源的肿瘤移植共存。这些小鼠在CD34干细胞移植后拥有类似人类的免疫系统，而免疫系统的重建水平与移植的CD34细胞数量无关。造血干细胞（HSC）移植中CD3细胞的污染率≤1.2%不会引发异常的T细胞成熟。鉴定出了不同的B细胞和T细胞分化阶段，以及表达TIGIT、PD-1或KLRG1的调节性T细胞（Tregs）和耗竭性T细胞。总体而言，使用流式细胞术对免疫细胞进行表征的标准化方案的应用将有助于更好地理解免疫肿瘤学过程。
