| 邹笑笑,祁玉娟.靶向CD47-SIRPα轴的晚期胃癌免疫治疗策略研究进展[J].肿瘤学杂志,2026,32(8):635-646. |
| 靶向CD47-SIRPα轴的晚期胃癌免疫治疗策略研究进展 |
| Research Progress on Immunotherapy Strategies for Advanced Gastric Cancer Targeting the CD47-SIRPα Axis |
| 投稿时间：2026-05-09 |
| DOI：10.11735/j.issn.1671-170X.2026.08.B003 |
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| 中文关键词: 胃肿瘤 分化簇47 信号调控蛋白α CD47?鄄SIRPα轴 免疫逃逸 免疫治疗 |
| 英文关键词:gastric neoplasms cluster of differentiation 47 signal-regulating protein α CD47-SIRPα axis 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） |
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| 中文摘要: |
| 摘 要：胃癌发病率和死亡率均较高，晚期胃癌患者治疗选择有限且预后不佳。尽管针对适应性免疫检查点的恶性肿瘤免疫疗法，如程序性死亡受体1，已经改变了肿瘤治疗的格局，但其在胃癌中的疗效仅限于少数患者，凸显了临床上对胃癌新疗法的急切需求。分化簇47（cluster of differentiation 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（signal-regulating protein 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其临床应用。全文对CD47-SIRPα信号进行介绍，并强调其在肿瘤免疫逃避中的作用及当前针对CD47-SIRPα轴的治疗策略研究进展，探讨如何通过双特异性抗体及联合免疫治疗策略突破治疗瓶颈，为晚期胃癌的精准免疫干预提供新视角。 |
| 英文摘要: |
| Abstract： Gastric cancer remains a leading cause of cancer-related mortality worldwide， with limited therapeutic options and poorly prognosis for advanced-stage patients. Although immune checkpoint inhibitors targeting adaptive immunity， such as anti-PD-1 agents， have revolutionized cancer treatment， their clinical benefit in gastric cancer is confined to a minority of patients， underscoring the urgent need for novel therapeutic approaches. cluster of differentiation 47(CD47)， a transmembrane protein widely overexpressed on tumor cells， delivers a“don’t eat me” signal by engaging signal-regulatory protein α (SIRPα) on phagocytes， thereby enabling immune evasion and contributing to treatment resistance. Disruption of the CD47-SIRPα interaction represents a promising strategy to restore macrophage-mediated phagocytosis and unleash antitumor adaptive immunity. However， off-target toxicities and the heterogeneity of the immunosuppressive tumor microenvironment pose major challenges to clinical translation. This review provides a comprehensive overview of the CD47-SIRPα signaling axis， highlights its mechanistic role in tumor immune escape， and summarizes current therapeutic modalities—including monoclonal antibodies， recombinant fusion proteins， bispecific antibodies， and combination regimens—with a focus on strategies to overcome existing bottlenecks. This review also discuss how rational combination with chemotherapy or other immune checkpoint inhibitors may potentiate efficacy and broaden the therapeutic window， offering new insights for precision immuno-intervention in advanced gastric cancer. |
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