小柯机器人

美国哥伦比亚大学Charles G. Drake、约翰霍普金斯大学Andrea Califano等研究人员合作发现与复发相关的肾肿瘤巨噬细胞。这一研究成果于2021年5月20日在线发表在国际学术期刊《细胞》上。

为了组装全面的透明细胞肾癌（ccRCC）肿瘤微环境图谱，研究人员对来自未经治疗的ccRCC切除肿瘤和邻近肿瘤组织的造血和非造血亚群进行了单细胞RNA测序（scRNA-seq）。研究人员利用VIPER算法对单细胞蛋白质活性进行定量，并通过与流式细胞术进行比较验证了该方法。该分析确定了关键的TME亚群及其主要调控因子和候选细胞之间的相互作用，从而揭示了临床相关人群，这些人群无法通过基因表达分析检测到。

具体来说，研究人员发现了以TREM2/APOE/C1Q上调为特征的肿瘤特异性巨噬细胞亚群，并通过空间分辨、定量多光谱免疫荧光进行了验证。在大型临床验证队列中，这些标志物在手术后复发的患者的肿瘤中显著丰富。因此，该研究确定了TREM2/APOE/C1Q阳性巨噬细胞浸润是ccRCC复发的潜在预后生物标志物，也是候选的治疗靶标。

据悉，ccRCC是一种异质性疾病，其术后病程可变。

附：英文原文

Title: Single-cell protein activity analysis identifies recurrence-associated renal tumor macrophages

Author: Aleksandar Obradovic, Nivedita Chowdhury, Scott M. Haake, Casey Ager, Vinson Wang, Lukas Vlahos, Xinzheng V. Guo, David H. Aggen, W. Kimryn Rathmell, Eric Jonasch, Joyce E. Johnson, Marc Roth, Kathryn E. Beckermann, Brian I. Rini, James McKiernan, Andrea Califano, Charles G. Drake

Issue&Volume: 2021-05-20

Abstract: Clear cell renal carcinoma (ccRCC) is a heterogeneous disease with a variable post-surgicalcourse. To assemble a comprehensive ccRCC tumor microenvironment (TME) atlas, we performedsingle-cell RNA sequencing (scRNA-seq) of hematopoietic and non-hematopoietic subpopulationsfrom tumor and tumor-adjacent tissue of treatment-naive ccRCC resections. We leveragedthe VIPER algorithm to quantitate single-cell protein activity and validated thisapproach by comparison to flow cytometry. The analysis identified key TME subpopulations,as well as their master regulators and candidate cell-cell interactions, revealingclinically relevant populations, undetectable by gene-expression analysis. Specifically,we uncovered a tumor-specific macrophage subpopulation characterized by upregulationof TREM2/APOE/C1Q, validated by spatially resolved, quantitative multispectral immunofluorescence.In a large clinical validation cohort, these markers were significantly enriched intumors from patients who recurred following surgery. The study thus identifies TREM2/APOE/C1Q-positivemacrophage infiltration as a potential prognostic biomarker for ccRCC recurrence,as well as a candidate therapeutic target.

DOI: 10.1016/j.cell.2021.04.038

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00573-0