细胞间通讯塑造了透明细胞肾细胞癌的肿瘤微环境并预测了临床结局。
Cell-cell communications shape tumor microenvironment and predict clinical outcomes in clear cell renal carcinoma.
机构信息
Department of Urology, The Second Affiliated Hospital of Chongqing Medical University, No1. Yixueyuan Rd, Yuzhong District, Chongqing, China.
First Clinical Institution, Chongqing Medical University, Chongqing, China.
出版信息
J Transl Med. 2023 Feb 10;21(1):113. doi: 10.1186/s12967-022-03858-x.
BACKGROUND
Cell-cell communications of various cell populations within tumor microenvironment play an essential role in primary tumor growth, metastasis evolution, and immune escape. Nevertheless, comprehensive investigation of cell-cell communications in the ccRCC (Clear cell renal carcinoma) microenvironment and how this interplay affects prognosis still remains limited.
METHODS
Intercellular communications were characterized by single-cell data. Firstly, we employed "CellChat" package to characterize intercellular communications across all types of cells in microenvironment in VHL mutated and non-mutated samples from 8 patients, respectively. And pseudotime trajectory analyses were performed with monocle analyses. Finally clinical prognosis and immunotherapy efficacy with different landscapes of intercellular interplay are evaluated by TCGA-KIRC and immunotherapy cohort.
RESULTS
Firstly, the VHL phenotype may be related to the intercellular communication landscape. And trajectory analysis reveals the potential relationship of cell-cell communication molecules with T cells and Myeloid cells differentiation. Furthermore, those molecules also correlate with the infiltration of T cells and Myeloid cells. A tumor cluster with highly expressed ligands was defined by quantitative analysis and transcription factor enrichment analysis, which was identified to be pivotal for intercellular communications in tumor microenvironment. Finally, bulk data indicates bulk that different clusters with different intercellular communications have significant predictive value for prognosis and distinguished immunotherapy efficiency.
CONCLUSIONS
The intercellular communication landscapes of VHL wild and VHL mutant ccRCC vary. Intercellular communications within the tumor microenvironment also influence T cell and myeloid cell development and infiltration, as well as predict clinical prognosis and immunotherapy efficacy in ccRCC.
背景
肿瘤微环境中各种细胞群体之间的细胞-细胞通讯对于原发性肿瘤生长、转移演变和免疫逃逸起着至关重要的作用。然而，对 ccRCC（透明细胞肾细胞癌）微环境中细胞-细胞通讯的全面研究以及这种相互作用如何影响预后仍然有限。
方法
通过单细胞数据来描述细胞间通讯。首先，我们使用“CellChat”包来分别对 8 名患者的 VHL 突变和非突变样本中的所有类型细胞之间的细胞间通讯进行特征描述。并通过 monocle 分析进行伪时间轨迹分析。最后，通过 TCGA-KIRC 和免疫治疗队列评估不同细胞间相互作用景观的临床预后和免疫治疗效果。
结果
首先，VHL 表型可能与细胞间通讯景观有关。轨迹分析揭示了细胞-细胞通讯分子与 T 细胞和髓样细胞分化的潜在关系。此外，这些分子也与 T 细胞和髓样细胞的浸润相关。通过定量分析和转录因子富集分析定义了一个高表达配体的肿瘤簇，该簇被认为是肿瘤微环境中细胞间通讯的关键。最后，批量数据表明，具有不同细胞间通讯的不同簇对预后有显著的预测价值，并区分了免疫治疗的效果。
结论
VHL 野生型和 VHL 突变型 ccRCC 的细胞间通讯景观不同。肿瘤微环境中的细胞间通讯也影响 T 细胞和髓样细胞的发育和浸润，并预测 ccRCC 的临床预后和免疫治疗效果。
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