Targeting cluster of differentiation 47 improves the efficacy of anti‑cytotoxic T‑lymphocyte associated protein 4 treatment via antigen presentation enhancement in pancreatic ductal adenocarcinoma

Song,Xifu; Lu,Zenghong; Xu,Jianqing

doi:10.3892/etm.2020.9054

Targeting cluster of differentiation 47 improves the efficacy of anti‑cytotoxic T‑lymphocyte associated protein 4 treatment via antigen presentation enhancement in pancreatic ductal adenocarcinoma

Authors:
- Xifu Song
- Zenghong Lu
- Jianqing Xu
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Affiliations: Department of General Surgery, People's Hospital of Jiyang County, Jinan, Shandong 250000, P.R. China, Department of Oncology, The First Affiliated Hospital of Gannan Medical College, Ganzhou, Jiangxi 341000, P.R. China, Department of General Surgery, Xi'an Gaoxin Hospital, Xi'an, Shaanxi 710075, P.R. China
Published online on: July 27, 2020 https://doi.org/10.3892/etm.2020.9054
Pages: 3301-3309

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Abstract

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 anti‑tumor 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, antigen‑presenting cells (macrophages and dendritic cells) in tumors with high CD47 expression demonstrated low CD80 and CD86 expression levels. In an in vitro co‑culture 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 antigen‑presenting cell tumor infiltration and T‑cell priming in tumor‑draining lymph nodes. Anti‑CD47 treatment appeared to enhance the efficacy of the approved immune checkpoint blockade agent anti‑cytotoxic T‑lymphocyte associated protein 4 (anti‑CTLA4) in suppressing PDAC development in a mouse model. Therefore, it was concluded that CD47 overexpression suppressed antigen presentation and T‑cell priming in PDAC. Anti‑CD47 treatment may enhance the efficacy of anti‑CTLA4 therapy and may therefore be a potential strategy for the treatment of PDAC patients in the future.

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