2. Academic Validation
  3. Cancer Immunotherapy via Disruption of Integrin αvβ3 and CD47 Costabilization on Cancer Cell Surface

Cancer Immunotherapy via Disruption of Integrin αvβ3 and CD47 Costabilization on Cancer Cell Surface

  • Adv Sci (Weinh). 2025 Oct 30:e01602. doi: 10.1002/advs.202501602.
Peng-Cheng Yu 1 2,  Chen-Xi Yue 1,  Wen-Zhong Dong 1,  Cui-Yun Hao 1,  Yi-Fan Qiao 1 2,  Di Liu 1,  Xin Zhang 1 3,  Qi Zhan 1,  Jia-Bao Yao 1,  Dong-Ping Wang 1,  Peng Cao 4,  Ying-Zhe Fan 2,  Ye Yu 1 3
Affiliations

Affiliations

  • 1 Schools of Basic Medicine and Clinical pharmacy, and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
  • 2 Interventional Cancer Institute of Chinese Integrative Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.
  • 3 Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, China.
  • 4 Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
PMID: 41168993 DOI: 10.1002/advs.202501602
Abstract

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 growth, without causing anemia or promoting angiogenesis. Thus, a stable interaction is identified between Integrin αvβ3 and CD47 on the Cancer cell membrane that facilitates immune evasion and demonstrates that targeting this interaction offers a safer therapeutic strategy for various tumors.

Keywords

CD47; cancer immunotherapy; immune checkpoint; integrin αvβ3; peptides.

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