Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, P. R. China.
J Clin Endocrinol Metab. 2020 Sep 1;105(9):e3207-23. doi: 10.1210/clinem/dgaa449.
The tumor immune microenvironment is associated with clinical outcomes and immunotherapy responsiveness.
To investigate the intratumoral immune profile of pituitary adenomas (PAs) and its clinical relevance and to explore a novel immune classification for predicting immunotherapy responsiveness.
DESIGN, PATIENTS, AND METHODS: The transcriptomic data from 259 PAs and 20 normal pituitaries were included for analysis. The ImmuCellAI algorithm was used to estimate the abundance of 24 types of tumor-infiltrating immune cells (TIICs) and the expression of immune checkpoint molecules (ICMs).
The distributions of TIICs differed between PAs and normal pituitaries and varied among PA subtypes. T cells dominated the immune microenvironment across all subtypes of PAs. The tumor size and patient age were correlated with the TIIC abundance, and the ubiquitin-specific protease 8 (USP8) mutation in corticotroph adenomas influenced the intratumoral TIIC distributions. Three immune clusters were identified across PAs based on the TIIC distributions. Each cluster of PAs showed unique features of ICM expression that were correlated with distinct pathways related to tumor development and progression. CTLA4/CD86 expression was upregulated in cluster 1, whereas programmed cell death protein 1/programmed cell death 1 ligand 2 (PD1/PD-L2) expression was upregulated in cluster 2. Clusters 1 and 2 exhibited a "hot" immune microenvironment and were predicted to exhibit higher immunotherapy responsiveness than cluster 3, which exhibited an overall "cold" immune microenvironment.
We summarized the immune profile of PAs and identified 3 novel immune clusters. These findings establish a foundation for further immune studies on PAs and provide new insights into immunotherapy strategies for PAs.
肿瘤免疫微环境与临床结局和免疫治疗反应性相关。
研究垂体腺瘤(PA)的肿瘤内免疫特征及其临床相关性,并探索一种新的免疫分类方法来预测免疫治疗反应性。
设计、患者和方法:纳入了 259 例 PA 和 20 例正常垂体的转录组数据进行分析。使用 ImmuCellAI 算法来估计 24 种肿瘤浸润免疫细胞(TICs)的丰度和免疫检查点分子(ICMs)的表达。
PA 和正常垂体之间 TICs 的分布不同,并且在 PA 亚型之间也存在差异。T 细胞在所有 PA 亚型中主导免疫微环境。肿瘤大小和患者年龄与 TIC 丰度相关,而促皮质素腺瘤中的泛素特异性蛋白酶 8(USP8)突变影响肿瘤内 TIC 分布。根据 TIC 分布,在 PA 中确定了 3 个免疫簇。每个 PA 簇都表现出独特的 ICM 表达特征,与肿瘤发生和进展相关的不同途径相关。CTLA4/CD86 在簇 1 中上调,而程序性细胞死亡蛋白 1/程序性细胞死亡 1 配体 2(PD1/PD-L2)在簇 2 中上调。簇 1 和簇 2 表现出“热”免疫微环境,预计比表现出总体“冷”免疫微环境的簇 3 具有更高的免疫治疗反应性。
我们总结了 PA 的免疫特征,并确定了 3 个新的免疫簇。这些发现为进一步研究 PA 的免疫提供了基础,并为 PA 的免疫治疗策略提供了新的见解。