PD-L1/p-STAT3 promotes the progression of NSCLC cells by regulating TAM polarization

被引:7
|
作者
Zhang, Rui [1 ,2 ,3 ]
Meng, Ziqi [1 ,2 ,3 ]
Wu, Xuwei [1 ,2 ,3 ]
Zhang, Meihua [4 ]
Piao, Zhengri [5 ]
Jin, Tiefeng [1 ,2 ,3 ]
机构
[1] Yanbian Univ, Med Coll, Dept Pathol, Gong Yuan Rd 977, Yanji 133002, Peoples R China
[2] Yanbian Univ, Med Coll, Canc Res Ctr, Gong Yuan Rd 977, Yanji 133002, Peoples R China
[3] Key Lab Sci & Technol Dept Jilin Prov, Yanji, Peoples R China
[4] Yanbian Univ Hosp, Dept Hlth Examinat Ctr, Yanji 133002, Peoples R China
[5] Yanbian Univ Hosp, Dept Radiol, Yanji, Peoples R China
基金
中国国家自然科学基金;
关键词
EMT; NSCLC; PD-L1; STAT3; TAM; M2; TUMOR-ASSOCIATED MACROPHAGES; LUNG-CANCER; MICROENVIRONMENT; METASTASIS;
D O I
10.1111/jcmm.17610
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
PD-L1 is closely related to the immune escape process of tumour cells, and targeted PD-L1 clinical immunotherapy has been implemented. However, whether PD-L1 is involved in TAM/M2 polarization in the TME of NSCLC and its specific mechanism remain unclear. In order to clarify the specific role of PD-L1 in NSCLC and to seek new treatments for NSCLC, we designed a series of experimental studies. After constructing the co-culture system and conditioned medium system, the proliferation, apoptosis, metastasis, angiogenesis, EMT process and stemness of NSCLC were detected by MTT, flow cytometry, Transwell, endothelial cell tube formation and western blot assays. The results showed that alpha PD-L1 reversed TAM/M2 polarization by suppressing STAT3 phosphorylation in TAM/M2, therapy inhibiting NSCLC cell migration, angiogenesis, EMT process and stemness. However, alpha PD-L1 had no effect on the proliferation and apoptosis abilities of NSCLC cells. In vivo experiments showed that alpha PD-L1 inhibited lung metastasis of NSCLC and reversed TAM/M2 polarization in TME. The study investigates the mechanism by which PD-L1 regulates TAMs polarization in TME and promotes malignant progression of NSCLC, providing a new theoretical basis for PD-L1 targeted therapy of NSCLC.
引用
收藏
页码:5872 / 5886
页数:15
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