胰腺癌肿瘤微环境与免疫治疗靶点的研究进展

Advances in tumor microenvironment and immunotherapy targets for pancreatic cancer

胰腺导管腺癌(PDAC)的发病率正在上升,预计将成为我国第二大癌症死亡原因。尽管人们对PDAC的了解取得了重大进展,但PDAC患者的生存率仍不尽如人意。PDAC的独特之处在于其明显的增生性改变,产生了一个由免疫细胞组成的大间质空间,包括免疫细胞、生长因子、细胞外基质和成纤维细胞,构成了肿瘤微环境(TME),可占肿瘤的15%~85%。TME在PDAC的肿瘤进展和化疗耐药中起着重要的作用,虽然对PDAC有许多有希望的靶点,利用TME使其进入早期临床试验,但尚无显著改善临床结果的治疗方案。目前正在研究多种靶向治疗方法有可能更好地结合基质耗竭、药物输送和免疫调节,从而在延长PDAC患者生存期方面取得进展。本综述将围绕TME免疫细胞、生长因子、细胞外基质和成纤维细胞以及TME成分产生的治疗靶点的研究进行讨论。

With the increasing incidence of pancreatic ductal adenocarcinoma(PDAC)in patients,it is estimated to be the second leading cause of cancer-related mortality in China.Despite the survival rate of PDAC patients is still poor.PDAC is characterized by the high complexity of stomal tissue,which includes immune cells,various growth factors,extracellular matrix and fibroblasts.TME accounts for about 15%-85% of the whole tumor component in PDAC.Emerging evidences have suggested that TME might play important roles in the tumor progress and drug-resistance of chemotherapy and a plenty of promising TME-related target molecules have been under early clinical trials.Nevertheless,there still lacks effective therapeutic treatments for improving the overall survival of PDAC patients.At present,progress has been made in the research of targeted therapies combined with matrix depletion,drug delivery and immunoregulation in PDACs.Thus,this review will focus on the latest progress in the fields of TME components including immune cells,growth factors,extracellular matrix and fibroblasts,as well as the therapeutic targets produced by these TME components.