CD47

Overview

CD47 is a cell-surface protein best known as a key innate immune checkpoint and a prominent “don’t eat me” signal. By engaging signal regulatory protein alpha (SIRPα) on myeloid cells, CD47 helps suppress phagocytosis and contributes to immune evasion. This function is especially relevant in cancer, where many tumors overexpress CD47 to reduce recognition and clearance by macrophages and other phagocytic cells.

Beyond its role in tumor biology, CD47 is also being explored as a target for immunomodulation in transplantation and regenerative medicine. Recent work has used CD47 blockade or CD47 engineering to alter local immune responses, enhance antitumor immunity, and improve graft survival. In these settings, CD47 is often studied alongside other immune pathways such as PD-L1, Fcγ receptors, and macrophage-mediated phagocytosis, reflecting its central position in checkpoint inhibitor.

Focus of Latest Publications

Recent publications demonstrate CD47 as a pivotal immune checkpoint that tumors exploit to evade phagocytosis and suppress anti-tumor immunity. CD47 functions as a "don't eat me" signal that engages signal regulatory protein alpha (SIRP-α) on myeloid cells, particularly macrophages, to inhibit their phagocytic activity. Multiple studies targeting the CD47-SIRP-α axis across diverse cancer types—including pancreatic cancer, melanoma, neuroblastoma, multiple myeloma, oral squamous cell carcinoma, and head and neck cancer—consistently demonstrate that blocking or reducing CD47 expression restores innate immune recognition and enables tumor cell killing.

CD47 blockade has been achieved through multiple therapeutic approaches, each designed to overcome the challenge of ubiquitous CD47 expression on healthy cells. Strategies include anti-CD47 antibodies, anti-SIRP-α antibodies such as LM-101, SIRP-α-displaying extracellular vesicles, anti-CD47 nanobodies delivered via oncolytic viruses or nanoparticle platforms, and tumor-targeting fusion proteins combining SIRP-α domains. Notably, engineered nanovesicles combining mucinase-degrading activity with anti-CD47 nanobodies enhanced CD47 accessibility by removing the protective tumor glycocalyx. A mechanistically distinct approach involved blocking CD47 maturation and surface translocation in the endoplasmic reticulum through disulfide bond reduction, achieving substantial reductions in CD47 surface expression.

These CD47-targeted strategies consistently enhanced macrophage-mediated phagocytosis and remodeled the tumor microenvironment. Studies demonstrated that CD47 blockade promoted macrophage polarization toward the pro-inflammatory M1 phenotype, increased innate immune activation, and enhanced CD8+ T cell infiltration and function. Combination approaches proved particularly effective: co-targeting CD47 with Cdk4/6 inhibitors, PD-L1 blockade, STING agonists, bortezomib, or oncolytic viruses yielded superior tumor control compared to monotherapies, with extended survival and durable anti-tumor responses.

Beyond cancer immunotherapy, recent findings revealed additional therapeutic applications of CD47 modulation. CD47 upregulation on platelets via LAV-BPIFB4 suppressed monocyte activation and inflammatory responses through selective MAPK pathway inhibition, offering potential benefits for inflammaging and cardiovascular disease. In transplantation, engineering islets to display CD47 created a tolerogenic microenvironment with increased myeloid-derived suppressor cells and T regulatory cells, enabling prolonged allograft survival without chronic immunosuppression. These studies highlight CD47 as a versatile immunological node with context-dependent roles in both tumor immunity and transplant tolerance.