CD47 is a cell-surface immune checkpoint protein that functions as a major “don’t eat me” signal, primarily by engaging sirp alpha to suppress macrophage phagocytosis and promote immune evasion. It is a therapeutic target in cancer immunotherapy, including melanoma, multiple myeloma, pancreatic cancer, and oral squamous cell carcinoma, where blocking the CD47-SIRPα axis can enhance antitumor immunity. Recent studies highlight multiple modalities for CD47 modulation, including anti-CD47 antibodies, an oncolytic vaccinia virus encoding a CD47 nanobody, and nanoplatforms that drive lysosomal internalization and degradation. Key mechanistic advances include ER-mediated disulfide bond reduction that blocks CD47 folding and surface translocation, and SIRPα-extracellular vesicles that mask tumor-cell CD47 to abrogate the checkpoint signal. Overall, CD47 is an immune evasion checkpoint with clinically relevant but still limited curative efficacy in some settings, motivating combination strategies such as imiquimod and targeted nanomaterials.
Cancer / Immunotherapy
- Anti-CD47 antibodies were used to block the CD47-sirp alpha interaction and inhibit tumor immune evasion in a “don’t eat me” checkpoint context. (PMID:41723989)
- A self-signal-suppressed MOF nanodrug improved melanoma immunotherapy via CD47 blockade in a 2026 Colloids and Surfaces B: Biointerfaces study. (PMID:41723989)
- An oncolytic vaccinia virus encoding a CD47 nanobody potentiated antitumor immunity in multiple myeloma in a 2026 iScience paper. (PMID:41858619)
- A ratio-tunable dual-peptide, ultrasound-assisted nanoplatform promoted personalized antitumor immunotherapy by targeting CD47 for lysosomal internalization and degradation. (PMID:41979280)
- SIRPα-extracellular vesicles masked tumor-cell CD47 to abrogate the checkpoint signal in a 2026 Journal of Nanobiotechnology study. (PMID:41957823)
Oral Squamous Cell Carcinoma
- CD47-targeted immunotherapy was discussed for oral squamous cell carcinoma, but the abstract noted that clinical curative efficacy remains limited. (PMID:41998354)
- Imiquimod enhanced the anti-tumor effects of CD47 targeting in oral squamous cell carcinoma in a 2026 Inflammation Research study. (PMID:41998354)
Pancreatic Cancer
- In pancreatic cancer, CD47 immune evasion was uncoupled by reprogramming endoplasmic reticulum disulfide reduction, linking redox control to checkpoint expression. (PMID:42015503)
- Electrons emitted from iodine-131 mediated continuous disulfide bond reduction, blocking CD47 folding and surface translocation and thereby reducing expression. (PMID:42015503)