Targeting CD47 Enhances the Efficacy of Anti-PD-1 and CTLA-4 in an Esophageal Squamous Cell Cancer Preclinical Model.
Esophageal squamous cell cancer is a highly aggressive cancer with a dismal 5-year survival rate. CD47 is a cell transmembrane protein that is involved in cell apoptosis, proliferation, adhesion, migration, and antigen presentation in the immune system. By interacting with signal regulatory protein-α expressed in antigen-presenting cells (APCs), CD47 acts as an antiphagocytic mechanism to inhibit APC-dependent antigen presentation. Overexpression of CD47 was found in various types of cancer. However, its role in esophageal squamous cell cancer is not yet clear. Anti-CD47 is an antagonist of CD47 signaling pathways by competing with its ligand. In the current study, we investigated the effects of anti-CD47 treatment on the antitumor immune response in an esophageal squamous cell cancer preclinical model. We found that anti-CD47 treatment enhanced proinflammatory responses and increased CD8+ T-cell infiltration in tumor tissue in the animal model. T cells in anti-CD47-treated tumors showed higher PD-1 and CTLA-4 expression, indicating T-cell activation and the rationale of combining anti-CD47 with anti-PD-1 and CLTA-4. The combinatory treatment showed the best antitumor response, implying a novel treatment strategy. The effects of anti-CD47 depended on dendritic cell function. In patient samples, expression of CD47 was negatively correlated with CD8+ T-cell infiltration in esophageal squamous cell cancer patients. Taken together, CD47 might be a novel target to enhance anti-PD-1 and CLTA-4 efficacy in esophageal squamous cell cancer.
Hua
H
Tao
Pudong
P
Qian
Feijiang
F
Wang
Hongliang
H
Yu
Yesong
Y
Guo
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D051928:CD47 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors* / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000378:metabolism*; D004195:Disease Models, Animal; D004938:Esophageal Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors* / Q000276:immunology; D015398:Signal Transduction; D014162:Transfection
D000906:Antibodies; D051928:CD47 Antigen; D060908:CTLA-4 Antigen; D061026:Programmed Cell Death 1 Receptor