CAR-T(CAR-T)细胞疗法在非肿瘤性疾病中的应用
Chimeric antigen receptor T (CAR-T) cell therapy in non-oncological diseases.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumor Microenvironment and Its Role in Cancer Progression: An Integrative Review.
Tumor Microenvironment and Its Role in Cancer Progression: An Integrative Review.
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肿瘤微环境(TME)在癌症进展、转移、免疫逃逸和治疗耐药中发挥关键作用。然而,现有文献往往分别研究其各组成部分。本综述综合呈现TME中成纤维细胞、免疫细胞和血管细胞、细胞外基质、细胞因子、外泌体及微生物群之间的动态相互作用。文章讨论上皮-间质转化、基质重塑和代谢重编程等经典机制,也探讨微生物组驱动的免疫调节和外泌体介导的治疗耐药等新兴模式。研究者结合单细胞及空间转录组学、3D生物打印和患者来源类器官模型等近期进展,考察肿瘤生态位的空间异质性及其时间演变。主要发现强调微生物组对免疫应答的影响,以及外泌体在转移耐药特征和调控细胞间信号中的作用。通过将分子机制与临床视角相结合,综述探讨靶向TME的转化策略,包括检查点抑制剂、基质调节剂、抗血管生成药物和工程化CAR-T 疗法。这一综合视角强调,应将癌症视为复杂、持续演化的生态系统,而非仅仅是细胞自主性疾病,并为精准肿瘤学提供基础框架,以破坏有害的TME相互作用并改善治疗效果和患者结局。
The tumor microenvironment (TME) plays a crucial role in cancer progression, metastasis, immune evasion, and treatment resistance.
However, the current literature often studies its components separately. This review offers an integrated view of the dynamic interactions among fibroblasts, immune and vascular cells, the extracellular matrix, cytokines, exosomes, and microbiota within the TME. It discusses classical mechanisms such as epithelial-mesenchymal transition, stromal remodeling, and metabolic rewiring alongside emerging paradigms like microbiome-driven immunomodulation and exosome-mediated therapy resistance. Spatial heterogeneity and the temporal evolution of the tumor niche are examined using recent advances in single-cell and spatial transcriptomics, 3D bioprinting, and patient-derived organoid models.
Key findings emphasize the microbiome's influence on immune responses and the role of exosomes in transferring resistance traits and regulating intercellular signaling. By connecting molecular insights with clinical perspectives, the review explores translational strategies targeting the TME, including checkpoint inhibitors, stromal modulators, anti-angiogenic agents, and engineered CAR-T therapies.
This comprehensive view highlights the importance of considering cancer as a complex, evolving ecosystem rather than just a cell-autonomous disease and provides a foundational framework for precision oncology approaches aimed at disrupting harmful TME interactions to improve therapeutic effectiveness and patient outcomes.
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