PDF(Pubmed)
Abstract：
Although adamantinomatous craniopharyngioma (ACP) is a tumour with low histological malignancy, there are very few therapeutic options other than surgery. ACP has high histological complexity, and the unique features of the immunological microenvironment within ACP remain elusive. Further elucidation of the tumour microenvironment is particularly important to expand our knowledge of potential therapeutic targets. Here, we performed integrative analysis of 58,081 nuclei through single-nucleus RNA sequencing and spatial transcriptomics on ACP specimens to characterize the features and intercellular network within the microenvironment. The ACP environment is highly immunosuppressive with low levels of T-cell infiltration/cytotoxicity. Moreover, tumour-associated macrophages (TAMs), which originate from distinct sources, highly infiltrate the microenvironment. Using spatial transcriptomic data, we observed one kind of non-microglial derived TAM that highly expressed GPNMB close to the terminally differentiated epithelial cell characterized by RHCG, and this colocalization was verified by asmFISH. We also found the positive correlation of infiltration between these two cell types in datasets with larger cohort. According to intercellular communication analysis, we report a regulatory network that could facilitate the keratinization of RHCG+ epithelial cells, eventually causing tumour progression. Our findings provide a comprehensive analysis of the ACP immune microenvironment and reveal a potential therapeutic strategy base on interfering with these two types of cells.
摘要：
尽管adamantinomatic颅咽管瘤（ACP）是一种组织学恶性程度较低的肿瘤，除了手术，很少有其他治疗选择。ACP具有较高的组织学复杂性，ACP中免疫微环境的独特特征仍然难以捉摸。进一步阐明肿瘤微环境对于扩大我们对潜在治疗靶标的认识尤为重要。这里,我们通过单核RNA测序和空间转录组学对ACP标本进行了58,081个细胞核的综合分析,以表征微环境中的特征和细胞间网络.ACP环境是高度免疫抑制的,具有低水平的T细胞浸润/细胞毒性。此外，肿瘤相关巨噬细胞（TAMs），来自不同的来源，高度渗透微环境。利用空间转录组数据，我们观察到一种非小胶质细胞来源的TAM，在以RHCG为特征的终末分化上皮细胞附近高表达GPNMB，并通过asmFISH验证了这种共定位。我们还发现在具有较大队列的数据集中这两种细胞类型之间的浸润正相关。根据细胞间通讯分析,我们报道了一个可以促进RHCG+上皮细胞角质化的调控网络，最终导致肿瘤进展。我们的发现提供了对ACP免疫微环境的全面分析，并揭示了基于干扰这两种类型细胞的潜在治疗策略。
