The CD47-SIRPα Axis in Cancer: Mechanisms of Immune Evasion and Innovative Therapeutic Approaches

The CD47-SIRPα axis plays a crucial role in tumor immune evasion by transmitting a "don’t eat me" sig- nal from cancer cells to macrophages, thereby inhibiting phagocytosis and facilitating tumor progression. CD47, a transmembrane protein overexpressed in a wide range of hematological and solid tumors, binds to signal regulatory protein alpha (SIRPα) on myeloid cells to suppress innate immune responses. This in- teraction has emerged as a promising therapeutic target, leading to the development of various strategies including monoclonal antibodies, fusion proteins, bispecific antibodies, and nanoparticle-based delivery systems aimed at disrupting CD47-SIRPα signaling. While promising, challenges such as off-tumor toxi- city, immune-related adverse effects, and tumor heterogeneity remain. This review discusses the molecu- lar biology of the CD47-SIRPα axis, its role in cancer immune evasion, current therapeutic developments, and emerging combination strategies, highlighting its potential as a next-generation target in cancer im- munotherapy.