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
  • 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.
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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