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:Immunotherapy in biliary tract cancer: reshaping the tumour microenvironment and advancing precision combination strategies.
胆道癌包括肝内胆管癌、肝外胆管癌和胆囊癌,因其侵袭性强且治疗选择有限,构成重大的临床挑战。
胆道癌包括肝内胆管癌、肝外胆管癌和胆囊癌,因其侵袭性强且治疗选择有限,构成重大临床挑战。尽管常用吉西他滨和顺铂等标准化疗,晚期胆道癌患者预后仍较差,原因是耐药发展迅速。近期免疫治疗进展,特别是免疫检查点抑制剂,显示出希望。然而,胆道癌患者应答率仍不理想,主要因为肿瘤微环境高度免疫抑制。该微环境包含肿瘤相关巨噬细胞、调节性 T 细胞和髓源性抑制细胞的复杂网络,共同促进免疫逃逸。本综述讨论驱动胆道癌的分子机制,重点关注基因改变和 TME 在免疫抑制中的作用。作者还考察免疫检查点抑制剂与化疗和靶向治疗联合的现有策略,这些方案较单药疗效更优。此外,综述探讨代谢调节、CAR-T 和 mRNA 疫苗等新兴治疗方法,这些方法正在重塑治疗格局。最后,作者强调个体化治疗策略和开发预测性生物标志物以指导治疗选择的必要性。未来研究应聚焦优化联合治疗、改进患者筛选并验证生物标志物,以改善胆道癌患者临床结局和生存。
Biliary tract cancer, which includes intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer, presents a significant clinical challenge because of its aggressive nature and limited therapeutic options. Although standard chemotherapy regimens, such as gemcitabine and cisplatin, are used, the prognosis for advanced biliary tract cancer patients remains poor due to the rapid development of resistance. Recently, advancements in immunotherapy, particularly immune checkpoint inhibitors, have shown promise. However, the response rate in patients with biliary tract cancer is still suboptimal primarily because of the highly immunosuppressive tumour microenvironment. This microenvironment includes a complex network of tumour-associated macrophages, regulatory T cells, and myeloid-derived suppressor cells, all of which contribute to immune evasion. In this review, we discuss the molecular mechanisms that drive biliary tract cancer, focusing on genetic alterations and the role of the TME in immune suppression. We also examine current combination strategies that integrate immune checkpoint inhibitors with chemotherapy and targeted therapies, which have demonstrated superior efficacy over monotherapy. Furthermore, we explore emerging therapeutic approaches, such as metabolic modulation, CAR-T-cell therapy, and mRNA vaccines, which are reshaping the treatment landscape. Finally, we highlight the need for personalized treatment strategies and the development of predictive biomarkers to guide therapy selection. Future research should focus on refining these combination therapies, optimizing patient selection, and validating biomarkers to improve clinical outcomes and survival in biliary tract cancer patients.
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