PD-L1 expression levels on tumor cells affect their immunosuppressive activity
Zheng, Yang1,2,3; Fang, You-Chen1,4; Li, Jing1
Source PublicationONCOLOGY LETTERS
AbstractProgrammed 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.
Keywordprogrammed cell death 1 programmed death-ligand 1 co-culture immunosuppression signaling pathway
Indexed BySCI
Funding ProjectShanghai Commission of Science and Technology (Shanghai, China)[16431901500]
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000503219600108
Original Document TypeArticle
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Cited Times [WOS]:0   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Corresponding AuthorLi, Jing
Affiliation1.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
First Author AffilicationSchool of Life Science and Technology
Recommended Citation
GB/T 7714
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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