生物力学调控肿瘤免疫治疗的机制与技术应用
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1.河南省消化器官移植重点实验室;2.郑州大学第一附属医院肝胆胰外科

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国家自然科学青年基金(32201068);河南省慈善联合总会・肝胆相照基金资助项目(GDXZ2023021)


Mechanisms and Technological Applications of Biomechanical Regulation in Tumor Immunotherapy
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1.Henan 2.Key 3.Laboratory 4.for 5.Digestive 6.Organ 7.Transplantation

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    摘要:

    肿瘤免疫治疗取得一定突破,但其临床疗效仍受限于肿瘤微环境(TME)的免疫抑制特性。既往研究聚焦于TME的生化调控网络,最新研究证明,生物力学因素通过重构细胞外基质(ECM)的物理特性与细胞力学感知系统,形成了独立于生化信号的免疫调控新维度。本文系统总结了生物力学与肿瘤免疫的交互作用机制,如力学信号通过整合素/YAP通路调控免疫检查点表达、T细胞迁移障碍及巨噬细胞极化等,为肿瘤的治疗提出"力学干预-免疫调控"的新思路。总结归纳力学敏感分子基因编辑,纳米颗粒及智能材料重塑TME等肿瘤免疫治疗前沿技术,提出"力学设计-精准递送-免疫调控"的系统解决方案,可能为开发肿瘤免疫治疗新方法提供新的理论依据。从临床转化视角看,生物力学机制的解析为克服免疫治疗耐药提供了新靶点(如YAP、PIEZO1),力学干预技术(如纳米颗粒软化基质、磁控机械力破坏肿瘤膜结构)可与现有免疫疗法(如CAR-T、免疫检查点抑制剂)协同增效,有望改善实体瘤患者治疗响应率。未来基于力学组学的个体化诊断与联合治疗策略,或将成为肿瘤精准免疫治疗的创新突破口。

    Abstract:

    Significant breakthroughs have been made in tumor immunotherapy, yet its clinical efficacy remains limited by the immunosuppressive nature of the tumor microenvironment (TME). While previous research has focused on the biochemical regulatory networks within the TME, recent studies have demonstrated that biomechanical factors, by remodeling the physical properties of the extracellular matrix (ECM) and the cellular mechanosensing system, constitute a new dimension of immune regulation independent of biochemical signals. This review systematically summarizes the mechanisms underlying the interplay between biomechanics and tumor immunity, such as the regulation of immune checkpoint expression via the integrin/YAP pathway, T cell migration disorders, and macrophage polarization, thereby proposing a novel "mechano-intervention?–?immune regulation" strategy for cancer therapy. We further summarize cutting-edge technologies in tumor immunotherapy, including mechanosensitive molecule gene editing, nanoparticles, and smart materials for remodeling the TME, and propose a systematic solution of "mechano-design?–?precision delivery?–?immune regulation", which may provide a new theoretical basis for developing novel tumor immunotherapies. From a clinical translational perspective, elucidating biomechanical mechanisms offers new targets (e.g., YAP, PIEZO1) to overcome immunotherapy resistance. Mechanical intervention techniques, such as nanoparticle-mediated matrix softening and magneto-mechanical disruption of tumor membrane structures, can synergize with existing immunotherapies (e.g., CAR-T, immune checkpoint inhibitors) to improve response rates in patients with solid tumors. In the future, individualized diagnosis and combination therapy strategies based on mechanomics may represent an innovative breakthrough in precision cancer immunotherapy.

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  • 收稿日期:2026-01-23
  • 最后修改日期:2026-04-11
  • 录用日期:2026-04-15
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