Dual SIRPα / CD47 Blockade Potentiates Monocyte-Driven Clearance of MCF-7 Breast Cancer Cells cancer research

Abstract

Background: Breast cancer (BC) is the most common cancer and a major cause of cancer-related death among women worldwide. In Iraq, it is the most prevalent malignancy in females. BC cells evade immune destruction through overexpression of CD47, a “don’t-eat-me” signal that binds SIRPα on monocytes and macrophages to inhibit phagocytosis. This study investigates CD47 inhibition in MCF-7 breast cancer cells and evaluates whether simultaneous SIRPα blockade enhances immune-mediated responses. It aims to assess the potential of treating MCF-7 cells in vitro by blocking the CD47–SIRPα interaction. To our knowledge, this is the first study in Iraq examining CD47 and SIRPα expression and their therapeutic potential in breast cancer cell lines.

Methods: MCF-7 cells were cultured and treated with anti-CD47 antibodies with or without monocytes pre-incubated with anti-SIRPα. Cell morphology was assessed using inverted microscopy. CD47 expression in MCF-7 cells and SIRPα in monocytes was confirmed by immunocytochemistry (ICC). Cell viability was measured using the MTT assay. Statistical analysis was performed using ANOVA with Tukey’s post-hoc test.

Results: ICC confirmed high expression of CD47 in MCF-7 cells and SIRPα in monocytes. Combined anti-CD47 and anti-SIRPα treatment showed a trend toward greater reduction in cell viability compared to single treatments, although not statistically significant. Anti-CD47 alone reduced cell viability by 47%, likely due to indirect or antibody-mediated effects. Morphological changes included cell shrinkage and loss of adhesion.

Conclusion: Dual blockade of CD47 and SIRPα showed a trend toward enhanced monocyte-mediated reduction in MCF-7 cell viability, suggesting the CD47/SIRPα axis as a potential immunotherapeutic target requiring further validation.