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Targeting cluster of differentiation 47 improves the efficacy of anticytotoxic Tlymphocyte associated protein 4 treatment via antigen presentation enhancement in pancreatic ductal adenocarcinoma

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Treatment with cluster of differentiation 47 (CD47) monoclonal antibody has exhibited promising antitumor effects in various preclinical cancer models. However, its role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In the present study, the CD47 expression level was measured in PDAC patient samples. The effects of CD47 on antigen presentation and antitumor immunity were evaluated using phagocytotic assays and animal models. The results indicated that CD47 was overexpressed in the tumor tissue of PDAC patients compared with that in normal adjacent tissues. In the human samples, antigenpresenting cells (macrophages and dendritic cells) in tumors with high CD47 expression demonstrated low CD80 and CD86 expression levels. In an in vitro coculture tumor cell system, CD47 overexpression was observed to inhibit the function of phagocytic cells. Furthermore, in a PDAC mouse model, CD47 overexpression was indicated to reduce antigenpresenting cell tumor infiltration and Tcell priming in tumordraining lymph nodes. AntiCD47 treatment appeared to enhance the efficacy of the approved immune checkpoint blockade agent anticytotoxic Tlymphocyte associated protein 4 (antiCTLA4) in suppressing PDAC development in a mouse model. Therefore, it was concluded that CD47 overexpression suppressed antigen presentation and Tcell priming in PDAC. AntiCD47 treatment may enhance the efficacy of antiCTLA4 therapy and may therefore be a potential strategy for the treatment of PDAC patients in the future.
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Document Type: Research Article

Affiliations: 1: Department of General Surgery, People's Hospital of Jiyang County, Jinan, Shandong 250000, P.R. China 2: Department of Oncology, The First Affiliated Hospital of Gannan Medical College, Ganzhou, Jiangxi 341000, P.R. China 3: Department of General Surgery, Xi'an Gaoxin Hospital, Xi'an, Shaanxi 710075, P.R. China

Publication date: October 1, 2020

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  • Experimental and Therapeutic Medicine aims to ensure the expedient publication, in both print and electronic format, of studies relating to biology, gene therapy, infectious disease, microbiology, molecular cardiology and molecular surgery. The journal welcomes studies pertaining to all aspects of molecular medicine, and studies relating to in vitro or in vivo experimental model systems relevant to the mechanisms of disease are also included.

    All materials submitted to this journal undergo the appropriate review via referees who are experts in this field. All materials submitted follow international guidelines with regard to approval of experiments on humans and animals.
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