|
| 靶向CD47-SIRPα轴的晚期胃癌免疫治疗新策略 |
| A new immunotherapy strategy for advanced gastric cancer targeting the CD47-SIRPα axis |
| 投稿时间：2026-05-09 修订日期：2026-06-16 |
| DOI： |
|
 |
| 中文关键词: 胃癌 CD47-SIRPα 免疫逃逸 免疫治疗 |
| 英文关键词:Gastric cancer CD47-SIRPα immune evasion immunotherapy |
| 基金项目:青海省“昆仑英才·高端创新创业人才”杰出人才项目(青人才字 [2025]17 号) |
|
| 摘要点击次数: 31 |
| 全文下载次数: 1 |
| 中文摘要: |
| 胃癌代表着一项重大的全球健康挑战,治疗选择有限且预后不佳。尽管针对适应性免疫检查点的癌症免疫疗法,如程序性死亡-1,已经改变了癌症治疗的格局,但其在GC中的疗效仅限于少数患者,凸显了临床上对新疗法的未满足需求。分化簇47(CD47),被称为“别吃我”信号,使肿瘤细胞通过结合骨髓细胞上的信号调控蛋白α(SIRPα)来规避吞噬作用,如巨噬细胞和树突状细胞。这种相互作用抑制了先天免疫反应,从而促进肿瘤的进展和对现有治疗的耐药性。靶向CD47–SIRPα轴可能是增强巨噬细胞介导吞噬作用并激活抗肿瘤适应性免疫的有效策略。然而,靶点外肿瘤毒性及免疫抑制肿瘤微环境的异质性限制了临床应用。本综述全面阐明了CD47–SIRPα信号通路,强调其在肿瘤免疫逃避中的作用及当前针对该轴的治疗策略进展,本文着重探讨如何通过双特异性抗体及联合免疫治疗策略突破上述瓶颈,为晚期胃癌的精准免疫干预提供新视角。 |
| 英文摘要: |
| Gastric cancer represents a major global health challenge, with limited treatment options and a poor prognosis. Although cancer immunotherapies targeting adaptive immune checkpoints, such as programmed death-1 (PD-1), have transformed the landscape of cancer treatment, their efficacy in gastric cancer (GC) is limited to a small subset of patients, highlighting the unmet clinical need for new therapies. Cytotoxicity-inhibitory receptor 47 (CD47), known as the “don’t eat me” signal, enables tumor cells to evade phagocytosis by binding to signal-regulating protein α (SIRPα) on immune cells, such as macrophages and dendritic cells. This interaction suppresses the innate immune response, thereby promoting tumor progression and resistance to existing therapies. Targeting the CD47–SIRPα axis may be an effective strategy to enhance macrophage-mediated phagocytosis and activate antitumor adaptive immunity. However, off-target tumor toxicity and the heterogeneity of the immunosuppressive tumor microenvironment have limited its clinical application. This review provides a comprehensive overview of the CD47–SIRPα signaling pathway, highlighting its role in tumor immune evasion and recent advances in therapeutic strategies targeting this axis. The article focuses on how bispecific antibodies and combination immunotherapy strategies can overcome these challenges, offering new perspectives for precision immunotherapy in advanced gastric cancer. |
|
在线阅读
查看/发表评论 下载PDF阅读器 |
|
|
|