Exosomal PD‑L1 promotes the formation of an immunosuppressive microenvironment in gastric diffuse large B‑cell lymphoma

Zeng,Hui; Wang,Jinfeng; Xu,Biaoming; Deng,Hongyu; Peng,Mingjing; Deng,Rilin; Shang,Song; Hu,Qi; Li,Junjun; Lin,Jinguan; Zhu,Haizhen; Li,Yajun; Zuo,Chaohui

doi:10.3892/or.2023.8525

Exosomal PD‑L1 promotes the formation of an immunosuppressive microenvironment in gastric diffuse large B‑cell lymphoma

Authors:
- Hui Zeng
- Jinfeng Wang
- Biaoming Xu
- Hongyu Deng
- Mingjing Peng
- Rilin Deng
- Song Shang
- Qi Hu
- Junjun Li
- Jinguan Lin
- Haizhen Zhu
- Yajun Li
- Chaohui Zuo
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Affiliations: Graduates Collaborative Training Base of Hunan Cancer Hospital, University of South China, Changsha, Hunan 410013, P.R. China, Department of Gastroduodenal and Pancreatic Surgery, Translational Medicine Research Center of Liver Cancer, Laboratory of Digestive Oncology, The Affiliated Cancer Hospital of Xiangya School of Medicine & Hunan Cancer Hospital, Hunan Cancer Institute, Central South University, Changsha, Hunan 410013, P.R. China, Institute of Pathogen Biology and Immunology of College of Biology, Hunan Provincial Key Laboratory of Medical Virology, State Key Laboratory of Chemo/Biosensing and Chemometrics, Hunan University, Changsha, Hunan 410082, P.R. China
Published online on: March 13, 2023 https://doi.org/10.3892/or.2023.8525
Article Number: 88
Copyright: © Zeng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gastric diffuse large B‑cell lymphoma (GDLBCL) is a common disease with an increasing incidence. However, the regulatory effect of exosomal programmed death‑ligand 1 (PD‑L1) on the immune microenvironment in GDLBCL is unclear. In the present study, the protein expression levels of exosomal PD‑L1 in the supernatants of cultured diffuse large B‑cell lymphoma (DLBCL) cells and the plasma of patients with GDLBCL was assessed using immunoblotting. Exosomes derived from DLBCL cells were cocultured with T lymphocytes or injected into tumor xenograft mice by tail vein injection. The relationship between the protein expression level of exosomal PD‑L1 in the plasma and the clinical characteristics and immune microenvironmental parameters of GDLBCL was evaluated using immunoblotting and immunohistochemistry. High levels of exosomal PD‑L1 were found in the supernatants of cultured DLBCL cells. Exosomes with high levels of PD‑L1 promoted growth of tumors formed by DLBCL cells in vivo and inhibited the proliferation of T lymphocytes. Notably, the protein expression level of PD‑L1 in plasma exosomes derived from GDLBCL patients was significantly higher than that of healthy individuals. High levels of PD‑L1 in plasma exosomes were significantly associated with international prognostic index score, pathological type and advanced Lugano stage, which might lead to the poor prognosis of GDLBCL. Moreover, a high level of PD‑L1 in plasma exosomes was significantly associated with an immunosuppressive microenvironment in GDLBCL. Therefore, the results of the present study indicated that exosomal PD‑L1 inhibited the proliferation of T lymphocytes and promoted the formation of an immunosuppressive microenvironment in GDLBCL. High expression of exosomal PD‑L1 may suggest a poor prognosis of GDLBCL, and exosomal PD‑L1 in plasma may be a new diagnostic indicator for GDLBCL.

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