PD-L1 expression levels on tumor cells affect their immunosuppressive activity
文献类型：期刊论文
| 作者 | Zheng, Yang2,3,4; Fang, You-Chen1,2; Li, Jing2
|
| 刊名 | ONCOLOGY LETTERS
 |
| 出版日期 | 2019-11-01 |
| 卷号 | 18期号:5页码:5399-5407 |
| 关键词 | programmed cell death 1 programmed death-ligand 1 co-culture immunosuppression signaling pathway |
| ISSN号 | 1792-1074 |
| DOI | 10.3892/ol.2019.10903 |
| 通讯作者 | Li, Jing(lijing@simm.ac.cn) |
| 英文摘要 | 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. |
| WOS关键词 | IMMUNE-CHECKPOINT INHIBITORS ; T-CELLS ; CO-STIMULATION ; CD28 ; ACTIVATION ; RECEPTOR ; TCR ; PROLIFERATION ; MECHANISMS ; BLOCKADE |
| 资助项目 | National Science & Technology Major Project: Key New Drug Creation and Manufacturing Program (Beijing, China)[2017ZX09101004-012-008] ; Personalized Medicines-Molecular Signature-based Drug Discovery and Development ; Chinese Academy of Sciences (Beijing, China)[XDA12040212] ; Shanghai Commission of Science and Technology (Shanghai, China)[16431901500] |
| WOS研究方向 | Oncology |
| 语种 | 英语 |
| WOS记录号 | WOS:000503219600108 |
| 出版者 | SPANDIDOS PUBL LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/282324]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Li, Jing |
| 作者单位 | 1.Shanghai Univ, Sch Life Sci, Shanghai 200444, Peoples R China 2.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 3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 4.Univ Chinese Acad Sci, Sch Pharm, Beijing 100049, Peoples R China |
| 推荐引用方式 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. |
入库方式： OAI收割
来源：上海药物研究所
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