TY  - EJOU
AU  - Tao, Hua 
AU  - Qian, Pudong 
AU  - Wang, Feijiang 
AU  - Yu, Hongliang 
AU  - Guo, Yesong 

TI  - Targeting CD47 Enhances the Efficacy of Anti-PD-1 and CTLA-4  in an Esophageal Squamous Cell Cancer Preclinical Model
T2  - Oncology Research

PY  - 2017
VL  - 25
IS  - 9
SN  - 1555-3906

AB  - 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-a expressed in antigenpresenting 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<sup>+</sup>
 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<sup>+</sup>
 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.
KW  - CD47; Dendritic cells; PD-1; CTLA-4; Esophageal squamous cell cancer

DO  - 10.3727/096504017X14900505020895