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髓源性抑制细胞的积累诱导调节性T细胞扩增并调节肺恶性肿瘤进展。

Myeloid‑derived suppressor cell accumulation induces Treg expansion and modulates lung malignancy progression.

作者信息

Wan Yinghua, Mu Xiangdong, Zhao Jingquan, Li Li, Xu Wenshuai, Zhang Mingqiang

机构信息

Department of Respiratory and Critical Care Medicine, Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, P.R. China.

出版信息

Biomed Rep. 2024 Mar 1;20(4):68. doi: 10.3892/br.2024.1754. eCollection 2024 Apr.

Abstract

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous family of myeloid cells that suppress T cell immunity in tumor-bearing hosts. The present study aimed to examine roles of T and MDSC subsets in lung malignancy. The study analyzed 102 cases with lung malignancy and 34 healthy individuals. Flow cytometry was performed for identification of T cell and MDSC subsets and their phenotypic characteristics in peripheral blood. The lung malignancy cases exhibited lower frequencies of granulocyte-like MDSCs (G-MDSCs) expressing PD-L2 and PD-L1 than healthy controls (P=0.013 and P<0.001, respectively). Additionally, there was a higher frequency of monocyte-like MDSCs (M-MDSCs) expressing PD-L1 in the peripheral blood of patients with lung malignancy than healthy controls (P<0.001). The frequencies of G-MDSCs and M-MDSCs were positively correlated with proportions of PD-1 and CTLA-4 regulatory T cells (Tregs). co-culture assay demonstrated M-MDSCs of lung malignancy enhanced naive T cell apoptosis and promoted Treg subset differentiation compared with M-MDSCs of healthy controls. The findings suggested accumulation of MDSC subsets in lung malignancy and MDSCs expressing PD-L2 and PD-L1 induced Treg expansion by binding to PD-1 on the surface of Tregs.

摘要

髓源性抑制细胞(MDSCs)是一类异质性的髓系细胞,可抑制荷瘤宿主的T细胞免疫。本研究旨在探讨T细胞和MDSC亚群在肺恶性肿瘤中的作用。该研究分析了102例肺恶性肿瘤患者和34名健康个体。采用流式细胞术鉴定外周血中T细胞和MDSC亚群及其表型特征。肺恶性肿瘤患者中表达PD-L2和PD-L1的粒细胞样MDSCs(G-MDSCs)频率低于健康对照(分别为P = 0.013和P < 0.001)。此外,肺恶性肿瘤患者外周血中表达PD-L1的单核细胞样MDSCs(M-MDSCs)频率高于健康对照(P < 0.001)。G-MDSCs和M-MDSCs的频率与PD-1和CTLA-4调节性T细胞(Tregs)的比例呈正相关。共培养试验表明,与健康对照的M-MDSCs相比,肺恶性肿瘤的M-MDSCs增强了幼稚T细胞凋亡并促进了Treg亚群分化。这些发现提示肺恶性肿瘤中MDSC亚群的积累,且表达PD-L2和PD-L1的MDSCs通过与Tregs表面的PD-1结合诱导Treg扩增。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/20f6/10963946/d2f8600cb3e0/br-20-04-01754-g00.jpg

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