Qu Peng, Zhang Hongyan
Department of Anesthesiology, Chengdu Wenjiang District People's Hospital, Chengdu, China.
Institute of Cardiovascular Diseases & Department of Cardiology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Front Immunol. 2025 Jul 31;16:1635388. doi: 10.3389/fimmu.2025.1635388. eCollection 2025.
Piezo1, a mechanosensitive ion channel, plays a pivotal and multifaceted role in tumor progression, immune evasion, and therapeutic resistance by transducing extracellular mechanical stimuli-such as matrix stiffness and fluid shear stress-into intracellular calcium influx. In tumor cells, Piezo1 promotes proliferation, invasion, and metastasis by activating oncogenic signaling and contributes to an immunosuppressive TME through regulation of cancer-associated fibroblasts (CAFs) and extracellular matrix (ECM) remodeling. In the immune compartment, Piezo1 integrates mechanical cues with metabolic and epigenetic reprogramming to orchestrate the functions of T cells, macrophages, and natural killer (NK) cells. Notably, Piezo1 deficiency impairs TH9 cell differentiation, diminishes T cell cytotoxicity, and enhances the activity of regulatory T cells (Tregs). Furthermore, Piezo1 expression correlates with distinct tumor immune phenotypes, such as "cold tumors," and with responses to immunotherapy, making it a promising predictive biomarker for treatment efficacy. Given its dual regulatory roles in tumor biology and immune modulation, targeting Piezo1-such as through combination with programmed death-1 (PD-1) blockade-offers a potential strategy to reverse immunosuppression and enhance antitumor immunity. This review summarizes emerging insights into Piezo1's role in cancer progression and immune regulation and highlights its translational potential as a novel target in cancer immunotherapy.
Piezo1是一种机械敏感离子通道，通过将细胞外机械刺激（如基质硬度和流体剪切应力）转化为细胞内钙内流，在肿瘤进展、免疫逃逸和治疗抗性中发挥关键且多方面的作用。在肿瘤细胞中，Piezo1通过激活致癌信号促进增殖、侵袭和转移，并通过调节癌症相关成纤维细胞（CAF）和细胞外基质（ECM）重塑，促成免疫抑制性肿瘤微环境（TME）。在免疫细胞区室中，Piezo1将机械信号与代谢和表观遗传重编程整合，以协调T细胞、巨噬细胞和自然杀伤（NK）细胞的功能。值得注意的是，Piezo1缺陷会损害TH9细胞分化，降低T细胞细胞毒性，并增强调节性T细胞（Treg）的活性。此外，Piezo1表达与不同的肿瘤免疫表型（如“冷肿瘤”）以及免疫治疗反应相关，使其成为治疗疗效的一个有前景的预测生物标志物。鉴于其在肿瘤生物学和免疫调节中的双重调节作用，靶向Piezo1（如通过与程序性死亡-1（PD-1）阻断联合使用）提供了一种逆转免疫抑制和增强抗肿瘤免疫力的潜在策略。本综述总结了对Piezo1在癌症进展和免疫调节中作用的新见解，并强调了其作为癌症免疫治疗新靶点的转化潜力。
