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

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

BIOMEDICAL REPORTS(2024)

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摘要
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). In vitro 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.
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关键词
lung cancer,myeloid-derived suppressor cell,T regulatory cell,PD-1,PD-L1,PD-L2
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