Lin Shaojian, Dai Yuting, Han Changxi, Han Tianyi, Zhao Linfeng, Wu Renyan, Liu Jianyue, Zhang Bo, Huang Ning, Liu Yanting, Lai Shujing, Shi Jintong, Wang Yu, Lou Meiqing, Xie Jing, Cheng Yijun, Tang Hao, Yao Hong, Fang Hai, Zhang Yan, Wu Xuefeng, Shen Lei, Ye Youqiong, Xue Li, Wu Zhe Bao
Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Neurosurgery, Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Genome Med. 2024 Apr 24;16(1):60. doi: 10.1186/s13073-024-01325-4.
Pituitary neuroendocrine tumors (PitNETs) are common gland neoplasms demonstrating distinctive transcription factors. Although the role of immune cells in PitNETs has been widely recognized, the precise immunological environment and its control over tumor cells are poorly understood.
The heterogeneity, spatial distribution, and clinical significance of macrophages in PitNETs were analyzed using single-cell RNA sequencing (scRNA-seq), bulk RNA-seq, spatial transcriptomics, immunohistochemistry, and multiplexed quantitative immunofluorescence (QIF). Cell viability, cell apoptosis assays, and in vivo subcutaneous xenograft experiments have confirmed that INHBA-ACVR1B influences the process of tumor cell apoptosis.
The present study evaluated scRNA-seq data from 23 PitNET samples categorized into 3 primary lineages. The objective was to explore the diversity of tumors and the composition of immune cells across these lineages. Analyzed data from scRNA-seq and 365 bulk RNA sequencing samples conducted in-house revealed the presence of three unique subtypes of tumor immune microenvironment (TIME) in PitNETs. These subtypes were characterized by varying levels of immune infiltration, ranging from low to intermediate to high. In addition, the NR5A1 lineage is primarily associated with the subtype characterized by limited infiltration of immune cells. Tumor-associated macrophages (TAMs) expressing CX3CR1, C1Q, and GPNMB showed enhanced contact with tumor cells expressing NR5A1 + , TBX19, and POU1F1, respectively. This emphasizes the distinct interaction axes between TAMs and tumor cells based on their lineage. Moreover, the connection between CX3CR1 macrophages and tumor cells via INHBA-ACVR1B regulates tumor cell apoptosis.
In summary, the different subtypes of TIME and the interaction between TAM and tumor cells offer valuable insights into the control of TIME that affects the development of PitNET. These findings can be utilized as prospective targets for therapeutic interventions.
垂体神经内分泌肿瘤（PitNETs）是常见的腺肿瘤，具有独特的转录因子。尽管免疫细胞在PitNETs中的作用已得到广泛认可，但对其精确的免疫环境及其对肿瘤细胞的控制了解甚少。
使用单细胞RNA测序（scRNA-seq）、批量RNA测序、空间转录组学、免疫组织化学和多重定量免疫荧光（QIF）分析PitNETs中巨噬细胞的异质性、空间分布和临床意义。细胞活力、细胞凋亡检测和体内皮下异种移植实验证实INHBA-ACVR1B影响肿瘤细胞凋亡过程。
本研究评估了来自23个PitNET样本的scRNA-seq数据，这些样本分为3个主要谱系。目的是探索这些谱系中肿瘤的多样性和免疫细胞的组成。对内部进行的scRNA-seq和365个批量RNA测序样本的分析数据显示，PitNETs中存在三种独特的肿瘤免疫微环境（TIME）亚型。这些亚型的特征是免疫浸润水平不同，从低到中再到高。此外，NR5A1谱系主要与免疫细胞浸润有限的亚型相关。表达CX3CR1、C1Q和GPNMB的肿瘤相关巨噬细胞（TAM）分别与表达NR5A1 +、TBX19和POU1F1的肿瘤细胞有增强的接触。这强调了基于谱系的TAM与肿瘤细胞之间不同的相互作用轴。此外，CX3CR1巨噬细胞与肿瘤细胞之间通过INHBA-ACVR1B的连接调节肿瘤细胞凋亡。
总之，TIME的不同亚型以及TAM与肿瘤细胞之间的相互作用为影响PitNET发展的TIME控制提供了有价值的见解。这些发现可作为治疗干预的潜在靶点。
