PD-L1 expression levels on tumor cells affect their immunosuppressive activity
Zheng, Yang1,2,3; Fang, You-Chen1,4; Li, Jing1
2019-11
发表期刊ONCOLOGY LETTERS
ISSN1792-1074
EISSN1792-1082
卷号18期号:5页码:5399-5407
发表状态已发表
DOI10.3892/ol.2019.10903
摘要

Programmed cell death 1 (PD-1) is an immuno-checkpoint receptor which is primarily expressed on T cells, monocytes, natural killer cells and macrophages. Programmed death-ligand 1 (PD-L1) is the primary ligand of PD-1 and is constitutively expressed on antigen presenting cells, mesenchymal stem cells and bone marrow-derived mast cells. In addition, PD-L1 is also expressed on a wide range of tumor cells, including lung cancer, breast cancer and melanoma. PD-1 and PD-L1 are important members of the immunoglobulin super-family and participate in immune regulation. In the present study, the immune-suppressive effects of a number of tumor cell lines were determined. The breast tumor cell lines MCF-7 and MDA-MB-231 displayed the largest inhibitory effects on T-cell activation and cytokine secretion in a co-culture system. The HepG2, A549 and A375 cells displayed limited inhibitory effects. MCF-7 and MDA-MB-231 cells expressed the highest level of PD-L1 among the cells used, which may explain their higher immuno-suppressive effects. Compound A0-L, a small molecule inhibitor of the PD-1/PD-L1 interaction, restored T cell functions. Additionally, it was demonstrated that the tumor cells with higher levels of PD-L1 expression suppressed signaling pathways involved in T-cell activation, such as the T-cell receptor- zeta chain of T cell receptor associated protein kinase ZAP70-RAS-GTPase-extracellular-signal-regulated kinases and CD28-PI3K-Akt serine/threonine kinases pathways. These findings suggest that tumor cells with higher expression levels of PD-L1 may exhibit higher immuno-suppressive activity, and that drugs targeting the PD-1/PD-L1 interaction may have improved therapeutic effects on tumors expressing higher levels of PD-L1.

关键词programmed cell death 1 programmed death-ligand 1 co-culture immunosuppression signaling pathway
收录类别SCI ; SCIE
语种英语
资助项目Shanghai Commission of Science and Technology (Shanghai, China)[16431901500]
WOS研究方向Oncology
WOS类目Oncology
WOS记录号WOS:000503219600108
出版者SPANDIDOS PUBL LTD
WOS关键词IMMUNE-CHECKPOINT INHIBITORS ; T-CELLS ; CO-STIMULATION ; CD28 ; ACTIVATION ; RECEPTOR ; TCR ; PROLIFERATION ; MECHANISMS ; BLOCKADE
原始文献类型Article
引用统计
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/104966
专题生命科学与技术学院_硕士生
通讯作者Li, Jing
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, Chinese Acad Sci Key Lab Receptor Res, Natl Ctr Drug Screening, 189 Guo Shou Jing Rd,Zhangjiang High Tech Pk, Shanghai 201203, Peoples R China
2.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China
3.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China
4.Shanghai Univ, Sch Life Sci, Shanghai 200444, Peoples R China
第一作者单位生命科学与技术学院
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Zheng, Yang,Fang, You-Chen,Li, Jing. PD-L1 expression levels on tumor cells affect their immunosuppressive activity[J]. ONCOLOGY LETTERS,2019,18(5):5399-5407.
APA Zheng, Yang,Fang, You-Chen,&Li, Jing.(2019).PD-L1 expression levels on tumor cells affect their immunosuppressive activity.ONCOLOGY LETTERS,18(5),5399-5407.
MLA Zheng, Yang,et al."PD-L1 expression levels on tumor cells affect their immunosuppressive activity".ONCOLOGY LETTERS 18.5(2019):5399-5407.
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