Cell–cell communications shape tumor microenvironment and predict clinical outcomes in clear cell renal carcinoma

Journal of Translational Medicine

Research

Qing Jiang¹  Liu-xun Chen¹  Jia-wu Wang¹  Shen-jie Zeng²  Xv-dong Liu²  Hai-bin Tang² 

[1] 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;

关键词: Cell–cell communications;    Tumor microenvironment;    Clear cell renal carcinoma;    Prognosis;    Immunotherapy;   

DOI  :  10.1186/s12967-022-03858-x

 received in 2022-06-24, accepted in 2022-12-28,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundCell–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.MethodsIntercellular 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.ResultsFirstly, 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.ConclusionsThe 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.

【 授权许可】

CC BY   
© The Author(s) 2023

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