PD‑L1 expression levels on tumor cells affect their immunosuppressive activity
- Yang Zheng
- You‑Chen Fang
- Jing Li
Affiliations: Chinese Academy of Sciences Key Laboratory of Receptor Research, National Center for Drug Screening, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P.R. China
- Published online on: September 20, 2019 https://doi.org/10.3892/ol.2019.10903
Copyright: © Zheng
et al. This is an open access article distributed under the
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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.