Is PD-L1 expressed on tumor cells?

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.

What regulates PD-L1 expression?

Regulation of PD-L1 expression in cancer cells at different levels. PD-L1 expression can be regulated by genomic amplification, transcriptional regulation, epigenetic regulation and transcriptional regulation.

How is PD-L1 upregulated on tumor cells?

Besides maintaining the stability of PD-L1 mRNA, PD-L1 expression can be upregulated by accelerating protein synthesis under the loss of PTEN in tumor cells, which leads to activation of the Akt/mTOR/S6K1 pathway and elevated PD-L1 protein translation rates, as reported for glioma (Parsa et al., 2007).

What is the importance of increased PD-L1 expression by a patient’s tumor with respect to treatment benefit with an immune checkpoint inhibitor?

With this background, PD-1 signaling represents a viable target for novel anti-cancer therapy. The development and clinical application of immune checkpoint inhibitors significantly enhance antitumor immunity, produce durable responses, and prolong survival in cancer patients.

What causes PD-L1 expression?

Generally, in the TME, the expression of PD-L1 is regulated by numerous factors, including inflammatory stimuli and oncogenic pathways at the levels of transcription, post-transcription, and post-translation. Exploring potential PD-L1 regulators helps select patients and overcome resistance to α-PD-1/PD-L1 treatments.

What induces PD-L1 expression?

IFN-g secreted by tumor-reactive T cells, signaling through the transcription factor STAT1, is the single major cytokine that induces PD-L1 protein expression.

How does PD-L1 therapy work?

When PD-1 binds to PD-L1, it basically tells the T cell to leave the other cell alone. Some cancer cells have large amounts of PD-L1, which helps them hide from an immune attack. Monoclonal antibodies that target either PD-1 or PD-L1 can block this binding and boost the immune response against cancer cells.

What is PD-L1 expressed by?

PD-L1 (ligand) is a membrane-bound protein that is expressed by various tumor cells. PD-L1 is not just expressed by tumor cells, but it may also be expressed by the lymphocytes that infiltrate tumors (51).

Where is PD-L1 expressed?

PD-L1, also known as CD274 and B7-H1, is a transmembrane protein commonly expressed on the surface of antigen presenting cells and tumor cells. PD-L1 specifically binds to its receptor, PD-1, which is expressed on the surface of immune-related lymphocytes, such as T cells, B cells, and myeloid cells (11, 12).

When is PD-L1 expressed?

PD-L1 is expressed on the surface of tumor cells and it is able to bind to PD-1 on the surface of activated T cells and B cells. The binding of PD-L1 to PD-1 leads to an immunosuppressive effect and allows the tumor to evade immune destruction (Swaika et al., 2015).