biostudies-literatureYu PCCAMS Innovation Fund for Medical Sciences"Xing Yao" Leading Scholars of China Pharmaceutical UniversityNational Natural Science Foundation of ChinaMedical Innovation and Development Project of Lanzhou UniversityInnovation and Entrepreneurship (Shuangchuang) Program of Jiangsu ProvinceChangsha "Jie Bang Gua Shuai" Major Science and Technology ProgramsNatural Science Foundation of Jiangsu Provincee01602https://www.ebi.ac.uk/biostudies/studies/S-EPMC12786276biostudies-literatureUnknown13(2)CD47/signal-regulatory protein α (SIRPα) signaling enables malignant cells to evade macrophage-mediated phagocytosis, offering a promising strategy for cancer therapy via immune checkpoint blockade. However, this strategy is widely debated due to several safety risks revealed by clinical studies, including anemia. Here, a CD47-SIRPα immune checkpoint treatment is investigated that mitigates anemic side effects by selectively interfering with the costabilization of CD47 and integrin αvβ3 on cancer cell surfaces, a phenomenon absent in erythrocytes. Multiplexed immunofluorescence analysis of 119 clinical breast cancer tissues reveals this costabilization. The engineered peptide PSFL-NK13 effectively disrupts this costabilization, which enhances macrophage phagocytosis and delays tumor growthAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Cancer Immunotherapy via Disruption of Integrin αvβ3 and CD47 Costabilization on Cancer Cell Surface.PMC12786276JSSCTD2023502019-I2M-5-074KQ2301004BK20202002YB M-05-02lzuyxcx-2022-15632371289Hao CYQiao YFWang DPYu PCDong WZYue CXFan YZZhang XZhan QYao JBLiu DCao PYu YfalseCancer Immunotherapy via Disruption of Integrin αvβ3 and CD47 Costabilization on Cancer Cell Surface.CD47/signal-regulatory protein α (SIRPα) signaling enables malignant cells to evade macrophage-mediated phagocytosis, offering a promising strategy for cancer therapy via immune checkpoint blockade. However, this strategy is widely debated due to several safety risks revealed by clinical studies, including anemia. Here, a CD47-SIRPα immune checkpoint treatment is investigated that mitigates anemic side effects by selectively interfering with the costabilization of CD47 and integrin αvβ3 on cancer cell surfaces, a phenomenon absent in erythrocytes. Multiplexed immunofluorescence analysis of 119 clinical breast cancer tissues reveals this costabilization. The engineered peptide PSFL-NK13 effectively disrupts this costabilization, which enhances macrophage phagocytosis and delays tumor growth2026-01-01T00:00:00Z2026 Jan2026-06-06T11:44:55.795Z2026-05-30T03:07:24.534ZS-EPMC127862764116899310.1002/advs.202501602