PDF(Pubmed)
Abstract：
Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer, accounting for over 75% of cases. The asymptomatic nature of the disease contributes to late-stage diagnoses and poor survival. Highly vascularized and immune infiltrated microenvironment are prominent features of ccRCC, yet the interplay between vasculature and immune cells, disease progression and response to therapy remains poorly understood. Using droplet-based single-cell RNA sequencing we profile 50,236 transcriptomes from paired tumor and healthy adjacent kidney tissues. Our analysis reveals significant heterogeneity and inter-patient variability of the tumor microenvironment. Notably, we discover a previously uncharacterized vasculature subpopulation associated with epithelial-mesenchymal transition. The cell-cell communication analysis reveals multiple modes of immunosuppressive interactions within the tumor microenvironment, including clinically relevant interactions between tumor vasculature and stromal cells with immune cells. The upregulation of the genes involved in these interactions is associated with worse survival in the TCGA KIRC cohort. Our findings demonstrate the role of tumor vasculature and stromal cell populations in shaping the ccRCC microenvironment and uncover a subpopulation of cells within the tumor vasculature that is associated with an angiogenic phenotype.
摘要：
透明细胞肾细胞癌（ccRCC）是肾癌的最常见形式，占病例的75%以上。该疾病的无症状性质导致晚期诊断和低生存率。高度血管化和免疫浸润的微环境是ccRCC的突出特征。然而脉管系统和免疫细胞之间的相互作用，疾病进展和对治疗的反应仍然知之甚少。使用基于液滴的单细胞RNA测序，我们分析了来自配对肿瘤和健康相邻肾组织的50,236个转录组。我们的分析揭示了肿瘤微环境的显着异质性和患者间变异性。值得注意的是,我们发现了一个与上皮-间质转化相关的先前未表征的血管亚群.细胞-细胞通讯分析揭示了肿瘤微环境中免疫抑制相互作用的多种模式，包括肿瘤脉管系统和基质细胞与免疫细胞之间的临床相关相互作用。参与这些相互作用的基因的上调与TCGAKIRC队列中较差的存活率相关。我们的发现证明了肿瘤脉管系统和基质细胞群体在塑造ccRCC微环境中的作用，并揭示了与血管生成表型相关的肿瘤脉管系统中的细胞亚群。
