用工程策略培育间充质干细胞以对抗癌症
Rearming mesenchymal stem cells with engineering strategies to combat cancer.
摘要(中文译文)
间充质基质/干细胞（MSCs）因其感知炎症信号并进入肿瘤邻近基质微环境的能力，作为有前景的肿瘤靶向递送载体正受到越来越多的关注。然而，它们在肿瘤微环境中的可塑性也使其能够启动促肿瘤程序，促进血管生成、基质重塑、免疫抑制、干性维持和治疗耐药。本综述总结了肿瘤招募MSCs所利用的分子“归巢层级”，主要通过CXCL12/CXCR4信号轴，并整合了与MSC驱动肿瘤进展相关的关键通路。重点在于“化敌为友”：将MSCs工程化为可编程的瘤内工厂和载体，以递送确定的抗癌有效载荷，包括自杀基因系统、促凋亡和抗血管生成效应分子、免疫刺激性细胞因子、局部免疫检查点阻断形式，以及结合瘤内扩增与免疫原性重塑的溶瘤病毒。此外，我们总结了旨在提高递送效率的抗原导向策略，以及精确控制抗肿瘤组分释放以尽量减少脱靶效应的策略。另外，我们讨论了利用MSCs进行抗肿瘤治疗所面临的巨大挑战。展望未来，通过先进的基因工程和联合治疗进一步优化基于MSC的抗肿瘤策略，有望显著提高其临床疗效。
Abstract
Mesenchymal stromal/stem cells (MSCs) are garnering increasing attention as promising tumor-targeted delivery vehicles owing to their ability to sense inflammatory signals and access tumor-adjacent stromal niches. However, their plasticity in the tumor microenvironment also enables pro-tumor programs that promote angiogenesis, matrix remodeling, immune suppression, stemness, and therapy resistance. This review summarizes the molecular "homing hierarchy" that tumors exploit to recruit MSCs, primarily through the CXCL12/CXCR4 signaling axis, and integrates key pathways implicated in MSC-driven tumor progression. The focus is on "turning enemies into allies": engineering MSCs into programmable intratumoral factories and carriers to deliver defined anticancer payloads, including suicide gene systems, pro-apoptotic and anti-angiogenic effectors, immune-stimulatory cytokines, localized checkpoint blockade formats, and oncolytic viruses that combine intratumoral amplification with immunogenic remodeling. Furthermore, we summarize antigen-directed strategies aimed at enhancing delivery efficacy and strategies to precisely control the release of antitumor components to minimize off-target effects. Additionally, we discuss the formidable challenges associated with harnessing MSCs for antitumor therapy. Looking ahead, further optimization of MSC-based antitumor strategies through advanced genetic engineering and combination therapies holds the potential to significantly enhance their clinical efficacy.
如何引用
AMA
Ting Yu, Sikan Jin, Rui Xu, Yaqi Zhang, Xianyao Wang. Rearming mesenchymal stem cells with engineering strategies to combat cancer.. Frontiers in immunology. 2026; doi:10.3389/fimmu.2026.1845224.
APA
Ting Yu, Sikan Jin, Rui Xu, Yaqi Zhang, Xianyao Wang (2026). Rearming mesenchymal stem cells with engineering strategies to combat cancer.. Frontiers in immunology. https://doi.org/10.3389/fimmu.2026.1845224
GB/T 7714
Ting Yu, Sikan Jin, Rui Xu, Yaqi Zhang, Xianyao Wang. Rearming mesenchymal stem cells with engineering strategies to combat cancer.[J]. Frontiers in immunology, 2026 doi:10.3389/fimmu.2026.1845224.
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