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外泌体 PD-L1 促进胃弥漫大 B 细胞淋巴瘤中免疫抑制微环境的形成。

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

机构信息

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.

出版信息

Oncol Rep. 2023 May;49(5). doi: 10.3892/or.2023.8525. Epub 2023 Mar 17.

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 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.

摘要

胃弥漫性大 B 细胞淋巴瘤(GDLBCL)是一种发病率不断增加的常见疾病。然而,外泌体程序性死亡配体 1(PD-L1)对 GDLBCL 免疫微环境的调节作用尚不清楚。在本研究中,通过免疫印迹法评估了培养的弥漫性大 B 细胞淋巴瘤(DLBCL)细胞上清液和 GDLBCL 患者血浆中外泌体 PD-L1 的蛋白表达水平。将源自 DLBCL 细胞的外泌体与 T 淋巴细胞共培养或通过尾静脉注射注入肿瘤异种移植小鼠。通过免疫印迹法和免疫组织化学法评估了血浆中外泌体 PD-L1 的蛋白表达水平与 GDLBCL 的临床特征和免疫微环境参数之间的关系。在培养的 DLBCL 细胞上清液中发现外泌体 PD-L1 水平较高。高 PD-L1 水平的外泌体促进了由 DLBCL 细胞形成的肿瘤的生长,并抑制了 T 淋巴细胞的增殖。值得注意的是,GDLBCL 患者血浆中外泌体 PD-L1 的蛋白表达水平明显高于健康个体。血浆中外泌体 PD-L1 水平较高与国际预后指数评分、病理类型和高级 Lugano 分期显著相关,这可能导致 GDLBCL 预后不良。此外,GDLBCL 中高水平的 PD-L1 与免疫抑制性微环境显著相关。因此,本研究结果表明,外泌体 PD-L1 抑制了 T 淋巴细胞的增殖并促进了 GDLBCL 中免疫抑制微环境的形成。外泌体 PD-L1 高表达可能提示 GDLBCL 预后不良,而血浆中外泌体 PD-L1 可能是 GDLBCL 的新诊断指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/371c/10073407/883a1a3c4f43/or-49-05-08525-g00.jpg

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