The tumor microenvironment in hepatocarcinoma:dissecting the functions of cancer-associated fibroblasts  

作　　者：Massimiliano Cadamuro Giorgia Nuozzi Paolo Simioni Luca Fabris 

机构地区：[1]Department of Medicine(DIMED),University of Padua,Padua 35128,Italy [2]School of Medicine and Surgery,University of Milan-Bicocca,Monza 20900,Italy [3]General Internal Medicine Unit,Padua University-Hospital,Padua 35128,Italy [4]Thrombotic and Haemorrhagic Disease Unit and Haemophilia Center,University of Padua,Padua 35128,Italy [5]Digestive Disease Section,Liver Center,Yale University,New Haven,CT 06519,US.

出　　处：《Hepatoma Research》2023年第1期52-69,共18页肝癌研究(英文版)

摘　　要：Hepatocellular carcinoma(HCC)is the most common primary liver malignancy,deriving from the neoplastic transformation of hepatocytes,most often forced to long-lasting regeneration by the cirrhotic background.HCC is an extremely aggressive tumor with still limited effective treatments,and is characterized by the presence of a very complex and multifaceted tumor microenvironment(TME).Among the variety of cell types populating the TME of HCC,cancer-associated fibroblasts(CAFs)are the most prevalent.CAFs are a specific population of fibroblasts in a persistent state of activation,with a high level of heterogeneity,partly dependent on a wide range of cell origin,which are endowed with a repertoire of functions,profoundly modulating the biology of the tumor.Given the close relationship of HCC with cirrhosis,CAFs are paradigmatic of the role played by activated fibroblasts in promoting the evolution of a chronic,non-resolving,fibro-inflammatory condition towards a neoplastic disease and its aggressive phenotype.In this review,we will discuss the most recent findings regarding the interplay of CAFs with the tumoral epithelial compartment,with the multiple cell elements of the TME(macrophages,neutrophils,myeloid-derived suppressor cells,vascular cells),and with the extracellular matrix.Finally,we will address the translational value of CAF manipulation in HCC to unveil possible ameliorations for the treatment of a still worrisome disease.

关 键 词：Cancer-associated fibroblasts tumor immune microenvironment CAF heterogeneity extracellular matrix remodeling tumor-associated macrophages 

分 类 号：R73[医药卫生—肿瘤]