小柯机器人

美国德克萨斯大学Raghu Kalluri研究团队发现，αSMA⁺肌成纤维细胞中的I型胶原缺失可增强免疫抑制作用并加速胰腺癌的进展 。这一研究成果于2021年3月4日在线发表在国际学术期刊《癌细胞》上。

研究人员表示，胰腺导管腺癌（PDAC）中的基质间质增生反应涉及I型胶原蛋白（Col1）的大量积累。但是，Col1在PDAC进展中的精确分子和机制贡献仍然未知。活化的星状细胞/αSMA⁺肌成纤维细胞是PDAC基质中Col1的主要贡献者。

研究人员使用自发性PDAC的双重重组酶遗传小鼠模型来敲除了成肌纤维细胞中的Col1。这导致总基质Col1含量显著降低，并加速了PanIN和PDAC的出现，从而降低了总生存期。Col1缺失通过SOX9导致癌细胞中Cxcl5上调。Cxcl5的增加与骨髓来源抑制细胞的招募和CD8⁺T细胞的抑制有关，可以通过联合靶向CXCR2和CCR2来减弱，进而抑制基质Col1缺失时加速的PDAC进展。

这些研究结果揭示了肌成纤维细胞来源的Col1在调节肿瘤免疫力和抑制PDAC进展中的基本作用。 

附：英文原文

Title: Type I collagen deletion in αSMA+ myofibroblasts augments immune suppression and accelerates progression of pancreatic cancer

Author: Yang Chen, Jiha Kim, Sujuan Yang, Huamin Wang, Chang-Jiun Wu, Hikaru Sugimoto, Valerie S. LeBleu, Raghu Kalluri

Issue&Volume: 2021-03-04

Abstract: Stromal desmoplastic reaction in pancreatic ductal adenocarcinoma (PDAC) involvessignificant accumulation of type I collagen (Col1). However, the precise molecularand mechanistic contribution of Col1 in PDAC progression remains unknown. Activatedpancreatic stellate cells/αSMA+ myofibroblasts are major contributors of Col1 in the PDAC stroma. We use a dual-recombinasegenetic mouse model of spontaneous PDAC to delete Col1 specifically in myofibroblasts.This results in significant reduction of total stromal Col1 content and acceleratesthe emergence of PanINs and PDAC, decreasing overall survival. Col1 deletion leadsto Cxcl5 upregulation in cancer cells via SOX9. Increase in Cxcl5 is associated with recruitment of myeloid-derived suppressor cells and suppressionof CD8+ T cells, which can be attenuated with combined targeting of CXCR2 and CCR2 to restrainaccelerated PDAC progression in the setting of stromal Col1 deletion. Our resultsunravel the fundamental role of myofibroblast-derived Co1l in regulating tumor immunityand restraining PDAC progression.

DOI: 10.1016/j.ccell.2021.02.007

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00109-4

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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