小柯机器人

英国癌症研究中心曼彻斯特研究所Claus Jrgensen研究组取得一项新突破。他们利用单细胞分析发现了具有抗肿瘤免疫能力的胰腺成纤维细胞谱系。2021年7月22日，国际学术期刊《癌细胞》在线发表了这一成果。

使用质谱流式细胞术，研究人员揭示了18个小鼠组织和5个自发性肿瘤模型的基质组成，主要是间充质表型。该分析揭示了跨组织和肿瘤的广谱基质异质性，并确定了胰腺导管腺癌中间充质和免疫细胞亚群之间的协调关系。CD105的表达与否可区分两种稳定且功能不同的胰腺成纤维细胞谱系，在小鼠和人健康组织以及肿瘤中也发现了这些细胞。CD105阳性的胰腺成纤维细胞促进肿瘤在体内的生长，而CD105阴性的成纤维细胞则具有高度的肿瘤抑制性。这种限制作用完全取决于功能适应性免疫。

总的来说，这些结果揭示了两种功能不同的胰腺成纤维细胞谱系，并重点描绘了间充质和免疫细胞相互作用在限制肿瘤生长方面的功能。

据悉，成纤维细胞具有广谱的转录异质性，但这些异质性细胞的功能和特征关系仍然未知。

附：英文原文

Title: Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity

Author: Colin Hutton, Felix Heider, Adrian Blanco-Gomez, Antonia Banyard, Alexander Kononov, Xiaohong Zhang, Saadia Karim, Viola Paulus-Hock, Dale Watt, Nina Steele, Samantha Kemp, Elizabeth K.J. Hogg, Joanna Kelly, Rene-Filip Jackstadt, Filipa Lopes, Matteo Menotti, Luke Chisholm, Angela Lamarca, Juan Valle, Owen J. Sansom, Caroline Springer, Angeliki Malliri, Richard Marais, Marina Pasca di Magliano, Santiago Zelenay, Jennifer P. Morton, Claus Jrgensen

Issue&Volume: 2021-07-22

Abstract: Fibroblasts display extensive transcriptional heterogeneity, yet functional annotation and characterization of their heterocellular relationships remains incomplete. Using mass cytometry, we chart the stromal composition of 18 murine tissues and 5 spontaneous tumor models, with an emphasis on mesenchymal phenotypes. This analysis reveals extensive stromal heterogeneity across tissues and tumors, and identifies coordinated relationships between mesenchymal and immune cell subsets in pancreatic ductal adenocarcinoma. Expression of CD105 demarks two stable and functionally distinct pancreatic fibroblast lineages, which are also identified in murine and human healthy tissues and tumors. Whereas CD105-positive pancreatic fibroblasts are permissive for tumor growth in vivo, CD105-negative fibroblasts are highly tumor suppressive. This restrictive effect is entirely dependent on functional adaptive immunity. Collectively, these results reveal two functionally distinct pancreatic fibroblast lineages and highlight the importance of mesenchymal and immune cell interactions in restricting tumor growth.

DOI: 10.1016/j.ccell.2021.06.017

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00339-1

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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