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

Abstract

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.

Transcript and protein signatures derived from shared molecular interactions across cancers are associated with mortality

“…The study was based on scRNA-seq, which allows the characterization of molecular changes in all cell types in a tumor. This may be advantageous because increasing evidence points to the pathogenic importance of multiple cell types in the TME 28,29 . This complexity leads to the problems of how best to organize systematically and prioritize mechanisms across cancers.…”

“…Recently, CCI and shared mechanisms were discussed for their potential use relates to cancer's clinical outcomes 29,33 . In this study, we hypothesized that this signature was associated with the mortality of cancer patients and tested the hypothesis in two independent cohorts (TCGA and UKBB).…”

Transcript and protein signatures derived from shared molecular interactions across cancers are associated with mortality

“…The study was based on scRNA-seq, which allows the characterization of molecular changes in all cell types in a tumor. This may be advantageous because increasing evidence points to the pathogenic importance of multiple cell types in the TME [ 28 , 29 ]. This complexity leads to the problems of how best to organize systematically and prioritize mechanisms across cancers.…”

“…Recently, CCI and shared mechanisms were discussed for their potential use relates to cancer’s clinical outcomes [ 29 , 32 ]. In this study, we hypothesized that this signature was associated with the mortality of cancer patients and tested the hypothesis in two independent cohorts (TCGA and UKBB).…”

Pan-cancer dissection of vasculogenic mimicry characteristic to provide potential therapeutic targets

“…Interactions between TME components and tumor cells constitute a focal point in cancer research ( Thorsson et al, 2018 ; Li et al, 2022 ; Chen L-X. et al, 2023 ; Chhabra and Weeraratna, 2023 ).…”