靶向巨噬细胞的癌症治疗策略
Macrophage-directed therapeutic strategies in cancer.
肿瘤相关巨噬细胞(TAMs)是肿瘤微环境的主要组成部分,具有显著的功能可塑性,根据所处的微环境信号,既可表现为促进肿瘤进展的免疫抑制细胞,也可表现为支持抗肿瘤免疫的免疫刺激细胞。
英文原题:Immunotherapeutic strategies in gastroenteropancreatic neuroendocrine neoplasms: present condition and future developments.
胃肠胰神经内分泌肿瘤(GEP-NENs)是异质性恶性肿瘤,常对标准治疗耐药。
胃肠胰神经内分泌肿瘤(GEP-NEN)具有异质性,且常对标准治疗耐药。免疫治疗是管理此类肿瘤的新前沿。本综述综合了免疫检查点抑制剂(ICI)、双特异性T细胞衔接器、嵌合抗原受体(CAR)T细胞疗法及溶瘤病毒疗法治疗GEP-NEN的临床和转化研究证据。我们考察关键抗原靶点(生长抑素受体、DLL3)及克服免疫抑制性肿瘤免疫微环境(TIME)的策略。单药ICI在高分化神经内分泌肿瘤(NET)中疗效有限,而双重免疫检查点阻断可使低分化神经内分泌癌(NEC)实现持久疾病控制。DLL3靶向双特异性抗体等靶向治疗方式已显示显著的早期疗效。此外,我们总结了高度协同的联合治疗方法,特别是免疫治疗与抗血管生成药物及肽受体放射性核素治疗(PRRT)的结合。以生物标志物为指导的在研试验和分子谱分析仍是优化患者选择及治疗顺序的关键。
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are heterogeneous malignancies frequently resistant to standard therapies. Immunotherapy represents a novel management frontier. This review synthesises clinical and translational evidence regarding immune checkpoint inhibitors (ICIs), bispecific T-cell engagers, chimeric antigen receptor (CAR) T-cell therapies, and oncolytic virotherapy in GEP-NENs. We examine critical antigenic targets (somatostatin receptors, DLL3) and strategies to overcome the immunosuppressive tumour immune microenvironment (TIME). While single-agent ICIs show modest efficacy in well-differentiated NETs, dual checkpoint blockade exhibits durable disease control in poorly differentiated NECs. Targeted modalities like DLL3-directed bispecific antibodies demonstrate significant early efficacy. Furthermore, we summarise highly synergistic combinatorial approaches, specifically integrating immunotherapy with anti-angiogenic agents and peptide receptor radionuclide therapy (PRRT). Ongoing biomarker-driven trials and molecular profiling remain essential to optimise patient selection and treatment sequencing.
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