低级别胶质瘤 (LGG) 是影响儿科患者 (pLGG) 的最常见脑肿瘤，BRAF 突变构成最常见的基因改变。在 pLGG 谱系中，大约 70%-80% 被诊断患有转化性多形性黄色星形细胞瘤 (PXA) 的儿科患者携带 BRAF V600E 突变。然而，神经胶质瘤 BRAF V600E 细胞对肿瘤浸润免疫细胞的调节作用及其对肿瘤进展的贡献仍不清楚。此外，与 BRAF 突变黑色素瘤的影响相比，BRAF 抑制剂治疗 pLGG 的功效有限。在这里，我们报告了一种新型的免疫活性 RCAS-BRAF V600E 小鼠神经胶质瘤模型。病理学评估表明该模型似乎与弥漫性胶质瘤和PXA的形态特征一致。我们的研究揭示了与肿瘤微环境 (TME) 内运输和激活增加相关的独特免疫细胞特征。有趣的是，TME 内的免疫系统激活还会产生与 CD8 T 细胞功能失调、免疫抑制性骨髓细胞和调节性 T 细胞增多相关的明显炎症反应。此外，我们的数据表明肿瘤诱发的炎症过程，例如细胞因子风暴。这些发现表明，临床前 BRAF V600E LGG 中肿瘤进展与 TME 内强烈的炎症反应之间存在复杂的相互作用，这可能会显着影响动物的生存。© 2024 作者。

Low-grade glioma (LGG) is the most common brain tumor affecting pediatric patients (pLGG) and BRAF mutations constitute the most frequent genetic alterations. Within the spectrum of pLGGs, approximately 70%-80% of pediatric patients diagnosed with transforming pleomorphic xanthoastrocytoma (PXA) harbor the BRAF V600E mutation. However, the impact of glioma BRAF V600E cell regulation of tumor-infiltrating immune cells and their contribution to tumor progression remains unclear. Moreover, the efficacy of BRAF inhibitors in treating pLGGs is limited compared with their impact on BRAF-mutated melanoma. Here we report a novel immunocompetent RCAS-BRAF V600E murine glioma model. Pathological assessment indicates this model seems to be consistent with diffuse gliomas and morphological features of PXA. Our investigations revealed distinct immune cell signatures associated with increased trafficking and activation within the tumor microenvironment (TME). Intriguingly, immune system activation within the TME also generated a pronounced inflammatory response associated with dysfunctional CD8+ T cells, increased presence of immunosuppressive myeloid cells and regulatory T cells. Further, our data suggests tumor-induced inflammatory processes, such as cytokine storm. These findings suggest a complex interplay between tumor progression and the robust inflammatory response within the TME in preclinical BRAF V600E LGGs, which may significantly influence animal survival.© 2024 The Authors.