Department of General Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China.
Endocr Relat Cancer. 2023 Feb 16;30(3). doi: 10.1530/ERC-22-0325. Print 2023 Mar 1.
Tumour microenvironment has been recognized as a crucial factor influencing disease progression. However, relevant features and functions are insufficiently understood in parathyroid neoplasia. Single-cell RNA sequencing was performed to profile the transcriptome of 27,251 cells from 4 parathyroid adenoma (PA) tissue samples. External transcriptomic datasets and immunofluorescence staining of a tissue microarray were set for expression validation. Eight major cell types and various subpopulations were finely identified in PA. We found that a subcluster of tumour endocrine cells with low copy number variation probably presented as a resting state. Diverse infiltrating immune cell subtypes were identified, constructing an immunosuppressive microenvironment. Tumour-associated macrophages, which indicated an anti-inflammatory phenotype, were significantly increased in PA. Inflammatory tumour-associated fibroblasts (iTAFs) were newly verified and highlighted on the role of stromal-immune crosstalk. Positive correlation between iTAFs and increased CD163+ macrophages was uncovered. Moreover, CXCL12 receptor signalling is important for tumour angiogenesis and immune infiltration. Our findings provide a comprehensive landscape interpreting tumour cell heterogeneity, cell diversity, and immune regulation in parathyroid neoplasia. The valuable resources may promote the understanding of parathyroid tumour microenvironment.
肿瘤微环境已被认为是影响疾病进展的关键因素。然而，甲状旁腺肿瘤的相关特征和功能尚未得到充分理解。我们对 4 个甲状旁腺腺瘤 (PA) 组织样本中的 27251 个细胞进行了单细胞 RNA 测序，以描绘其转录组图谱。我们设置了外部转录组数据集和组织微阵列的免疫荧光染色，以进行表达验证。在 PA 中精细鉴定了 8 种主要细胞类型和各种亚群。我们发现，肿瘤内分泌细胞的一个亚群具有低拷贝数变异，可能呈现静止状态。鉴定出了多种浸润性免疫细胞亚群，构成了免疫抑制性微环境。肿瘤相关巨噬细胞（TAMs）显著增加，其表现出抗炎表型。我们新验证并强调了炎性肿瘤相关成纤维细胞（iTAFs）在基质-免疫相互作用中的作用。发现 iTAFs 与增加的 CD163+巨噬细胞之间存在正相关。此外，CXCL12 受体信号对肿瘤血管生成和免疫浸润很重要。我们的研究结果提供了一个全面的景观，解释了甲状旁腺肿瘤中的肿瘤细胞异质性、细胞多样性和免疫调节。这些有价值的资源可能有助于加深对甲状旁腺肿瘤微环境的理解。
