决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Tumor stroma and its role in therapy resistance: mechanisms and therapeutic opportunities.
靶向肿瘤基质通过改善药物递送、同时推进对肿瘤生物学和治疗耐药的理解,代表肿瘤学中一个有前景的方向,支持开发更有效、更具情境针对性的疗法。
引言:肿瘤微环境(TME)由癌细胞、免疫细胞、基质细胞及细胞外基质构成,在肿瘤起始、进展、转移和治疗耐药中发挥关键作用。尽管免疫检查点抑制剂和CAR-T细胞等免疫靶向疗法改变了癌症治疗,基质细胞日益被视为肿瘤生物学的重要调节者。 综述范围:基质细胞调控肿瘤代谢、免疫逃逸、血管生成和药物耐药。它们可来源于周围组织或细胞转分化,并可根据具体情境发挥促肿瘤或抑肿瘤作用。目前策略包括靶向透明质酸和层粘连蛋白等基质成分以递送药物,或重塑基质以改善治疗应答。基质靶向递送系统可提高穿透性、特异性、安全性和生物相容性,并显示出良好的临床结局。癌症相关成纤维细胞、间充质干细胞、肿瘤相关脂肪细胞、内皮细胞和周细胞也构成新兴治疗靶点。通过PubMed、Scopus和Web of Science检索截至2025年4月发表的相关研究。 专家观点:通过改善药物递送,同时深化对肿瘤生物学和治疗耐药的理解,靶向肿瘤基质是肿瘤学中一个有前景的方向,可支持开发疗效更好且情境特异的治疗。
INTRODUCTION: The tumor microenvironment (TME), composed of cancer, immune, and stromal cells together with the extracellular matrix, plays critical roles in tumor initiation, progression, metastasis, and therapeutic resistance. Although immune-targeted therapies, including immune checkpoint inhibitors and CAR-T cells, have transformed cancer treatment, stromal cells are increasingly recognized as key regulators of tumor biology. AREAS COVERED: Stromal cells regulate tumor metabolism, immune evasion, angiogenesis, and drug resistance. They originate from surrounding tissues or cellular transdifferentiation and may exert tumor-promoting or tumor-suppressive effects depending on context. Current strategies target stromal components such as hyaluronic acid and laminin for drug delivery or remodel the stroma to improve therapeutic response. Stromal-targeted delivery systems enhance penetration, specificity, safety, and biocompatibility, with promising clinical outcomes. Cancer-associated fibroblasts, mesenchymal stem cells, tumor-associated adipocytes, endothelial cells, and pericytes also represent emerging therapeutic targets. Relevant studies published through April 2025 were identified using PubMed, Scopus, and Web of Science. EXPERT OPINION: Targeting the tumor stroma represents a promising direction in oncology by improving drug delivery while advancing understanding of tumor biology and treatment resistance, supporting development of more effective, context-specific therapies.
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