肿瘤微环境的靶向和重塑策略

Strategies for targeting and remodeling tumor microenvironment

肿瘤微环境(tumor microenvironment,TME)由异常的肿瘤血管、细胞外基质组分、内皮细胞、周细胞、肿瘤相关成纤维细胞、平滑肌细胞和免疫细胞组成。TME在肿瘤的发生、生长和转移中起着至关重要的作用。TME中异常的肿瘤血管系统、细胞外基质组分及丰富的间质细胞等,影响了药物在肿瘤组织的分布和渗透,其免疫抑制状态也是导致包括免疫治疗在内的多种抗肿瘤失败的重要原因之一。近年来,许多研究致力于通过靶向和重塑TME以提高治疗效果。本文综述了基于乏氧状态、肿瘤血管系统、肿瘤相关成纤维细胞、细胞外基质组分、肿瘤相关巨噬细胞和树突细胞的靶向和重塑策略最新研究进展,并对其中存在的问题及未来的发展进行讨论。

Tumor microenvironment(TME)is composed of abnormal tumor vasculature,extracellular matrix components,endothelial cells,pericytes,tumor associated fibroblasts,smooth muscle cells and immune cells,which is characterized by hypoxia,acidosis and high interstitial fluid pressure.Hypoxia and acidosis within the TME trigger an adjustment of the extracellular matrix(ECM),a response from neighbor stromal cells(e.g.,fibroblasts)and immune cells(lymphocytes and macrophages),inducing tumor growth,angiogenesis,and ultimately,resulting in metastasis.What's more,the components of TME including abnormal tumor vasculature,rich composition of the ECM,and abundant stroma cells impair tumoral distribution and penetration of the drugs.At the same time,this stromal microenvironment plays a vital role in creating an immunosuppressive environment.Over the past years,more and more researches focus on targeting and remolding TME to improve therapeutic effects against tumors.Herein,we reviewed current strategies developed to target and remodel TME,including modulating tumor hypoxia,tumor vasculature,tumor associated fibroblasts,extracellular matrix components,tumor associated macrophage phenotypes and dendritic cells.Also,potential problems and future directions are pointed out in this review.