卵巢颗粒细胞瘤（GCTs）来源于颗粒细胞（GCs），是人类最常见的性索间质肿瘤。然而，它们发育调节和分子机制的病因基础大多数仍是未知。在本研究中，我们结合了一个多重荧光报告小鼠模型和条件性敲除小鼠模型，其中肿瘤抑制基因Pten和p27在GCs中被删除，进行突变GCs的细胞系追踪。我们发现只有具有相当数量突变GCs的卵巢中的30％发展成为从单个突变GC衍生的GCTs。深入的肿瘤发生过程的分子分析证明，免疫逃避基因Cd24a和Cd47的上调，在一定程度上导致突变GCs向GCTs的过渡。因此，使用Cd47抑制剂RRX-001治疗被测试，并发现在体内有效地抑制了GCTs的生长。综上所述，我们的研究揭示了通过CD24 / CD47上调的免疫逃避机制对GCT形成的作用，为未来的GCT临床治疗提供了启示。©2023年作者。

Ovarian granulosa cell tumors (GCTs) originate from granulosa cells (GCs) and represent the most common sex cord-stromal tumor in humans. However, the developmental regulations and molecular mechanisms underlying their etiology are largely unknown. In the current study, we combined a multi-fluorescent reporter mouse model with a conditional knockout mouse model, in which the tumor suppressor genes Pten and p27 were deleted in GCs, to perform cell lineage tracing of mutant GCs. We found that only 30% of ovaries with substantial mutant GCs developed into GCTs that derived from a single mutant GC. In-depth molecular analysis of the process of tumorigenesis demonstrated that up-regulation of immune evasion genes Cd24a and Cd47 led, in part, to the transition of mutant GCs to GCTs. Therefore, treatment with the Cd47 inhibitor RRX-001 was tested and found to efficiently suppress the growth of GCTs in vivo. Together, our study has revealed an immune evasion mechanism via CD24/CD47 upregulation to GCT formation, shedding light on the future potential clinical therapies for GCTs.© 2023. The Author(s).