biostudies-literatureMonther ANational Cancer Institutee0328031https://www.ebi.ac.uk/biostudies/studies/S-EPMC12912607biostudies-literatureUnknown21(2)Head and neck squamous cell carcinoma (HNSCC) is a significant cause of morbidity and mortality worldwide, with limited treatment options for patients with locally advanced disease. CD47 immune checkpoint inhibitors have been used to block the CD47/SIRPa interaction that inhibits antigen-presenting cell phagocytosis, thereby enhancing antigen presentation to cytotoxic T-cells, and have shown promise in combination with anti-PD1 immunotherapy in tumors, including recurrent/metastatic HNSCC. We found that CD47 expression is associated with poor prognosis in HNSCC and explored the anti-tumor activity of an anti-CD47 fusion protein in combination with anti-PD1 and lymphatic-sparing radiotherapy in a locally advanced HNSCC model. In the 4MOSC1 syngeneic HPV-negative HNSCC mouse model, ALX301 (aPloS oneCD47 blockade (ALX301) enhances immunoradiotherapy response in HPV negative head and neck squamous cell carcinoma.PMC12912607R01CA281285Al-Msari RGutkind SPhilips CTang CDecker KSen PCalifano JMonther ASaddawi-Konefka RFassardi SSharabi AMiyauchi SRoy SMohammadzadeh PJones RWu XfalseCD47 blockade (ALX301) enhances immunoradiotherapy response in HPV negative head and neck squamous cell carcinoma.Head and neck squamous cell carcinoma (HNSCC) is a significant cause of morbidity and mortality worldwide, with limited treatment options for patients with locally advanced disease. CD47 immune checkpoint inhibitors have been used to block the CD47/SIRPa interaction that inhibits antigen-presenting cell phagocytosis, thereby enhancing antigen presentation to cytotoxic T-cells, and have shown promise in combination with anti-PD1 immunotherapy in tumors, including recurrent/metastatic HNSCC. We found that CD47 expression is associated with poor prognosis in HNSCC and explored the anti-tumor activity of an anti-CD47 fusion protein in combination with anti-PD1 and lymphatic-sparing radiotherapy in a locally advanced HNSCC model. In the 4MOSC1 syngeneic HPV-negative HNSCC mouse model, ALX301 (a2026-01-01T00:00:00Z20262026-07-16T05:14:32.382Z2026-07-09T10:38:16.182ZS-EPMC129126074170171310.1371/journal.pone.0328031