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

## TL;DR

A new cancer therapy disrupts a specific protein interaction on cancer cells to boost immune response without causing anemia.

## Contribution

A novel peptide is developed to selectively disrupt CD47 and integrin αvβ3 costabilization, offering a safer immunotherapy approach.

## Key findings

- The interaction between CD47 and integrin αvβ3 is specific to cancer cells and absent in erythrocytes.
- The peptide PSFL-NK13 enhances macrophage phagocytosis and delays tumor growth without causing anemia.
- Targeting this interaction provides a safer alternative to conventional CD47-targeting therapies.

## 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.

This study identifies a cancer‐specific interaction between CD47 and integrin αvβ3 that facilitates immune evasion. A rationally designed peptide, PSFL‐NK13, disrupts this axis, enhancing macrophage‐mediated phagocytosis and suppressing tumor growth without inducing anemia. These findings establish a safer immune checkpoint strategy distinct from conventional CD47‐targeting therapies.