摘要
肿瘤成纤维样细胞是肿瘤间质内数量最多的细胞组分.不同类型实体肿瘤的成纤维样细胞来源有所不同,但均对肿瘤微环境的塑造起到至关重要的作用.其可以大量分泌细胞外基质,促进肿瘤血管新生,阻碍药物输运,阻止免疫细胞的肿瘤浸润,增强肿瘤的化疗及免疫治疗耐受等.因此,针对肿瘤成纤维样细胞促进肿瘤发展的功能进行调控,可重塑肿瘤微环境,提高肿瘤的治疗效果.本文简要介绍了肿瘤成纤维样细胞在肿瘤微环境中的重要作用,并重点介绍基于纳米药物精准调控肿瘤成纤维样细胞的研究进展,为继续开发基于调控肿瘤成纤维样细胞的肿瘤治疗策略提供思路.
Abstract
Tumor tissues have a complex microenvironment containing various cellular and non-cellular components.Cancer-associated fibroblasts(CAFs)are the largest population in the stroma.CAFs can originate from many cell types,including native fibroblasts,stellate cells,epithelial cells,endothelial cells,and mesenchymal stem cells.We think the more precise description of CAFs is"tumor fibroblast-like cells"(TFLCs).TFLCs play pivotal roles in shaping the tumor microenvironment as the primary stromal cells through secreting various growth factors and extracellular matrix.For example,TFLCs secret vascular endothelial growth factor(VEGF)to regulate tumor angiogenesis,CXCL12 to upregulate anti-apoptotic proteins like Bcl-2 and survivin expression in tumor cells.TFLCs also establish physiological barriers within tumor tissues.For instance,TFLCs promote fabricating tumor extracellular matrix by secreting abundant collagens and fibronectin,which hinders the infiltration of immune cells and the penetration of anti-tumor drugs,and therefore impeding the efficacy of chemotherapy and immunotherapy.Consequently,modulating TFLCs can contribute to effectively suppressing tumor development and improving treatment outcomes.Due to the abundant distribution of TFLCs around tumor blood vessels,nanomedicines may first come into contact with TFLCs when they permeate from tumor blood vessels.Therefore,this provides relatively convenient conditions for utilizing nanomedicines to regulate TFLCs.The rational design of nanomedicines enables the targeted delivery of therapeutic agents to TFLCs,facilitating the modulation of TFLC functions at the genetic and/or molecular levels.Meanwhile,the phenotype,genes and protein levels of TFLCs could be changed after treatment,which may also provide new targets for nanomedicines.In this review,we give a concise overview of the origins and functions of TFLCs,and we focus on highlighting recent research progress on using nanomedicines to regulate TFLCs,such as loading chemotherapy drugs to directly deplete TFLCs,loading anti-fibrosis drugs to modulate TFLC function,and employing antibodies or nucleic acid drugs to precisely regulate signaling pathways in TFLCs.All these strategies prove that regulating TFLCs can enhance the efficacy of cancer treatment.To further develop this field,we need to pay more attention to the subtypes of TFLCs,especially the subtype population and signaling pathway changes of TFLCs before and after the treatments(chemotherapy,radiotherapy and/or immunotherapy).Since TFLCs are the largest stromal cell population in the tumor microenvironment,we may utilize TFLCs as a factory to produce drugs or antigens by using gene editing techniques to enhance the therapeutic efficacy.Overall,this review can provide feasible references for improving the treatment of solid tumors through regulating the tumor microenvironment.
NETL
NSTL
维普
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