Programmed-death ligand 1 (PD-L1), also known as CD274 and B7-H1, is a 33 kDa type I glycoprotein containing 290 amino acids (aa) belonging to the protein B7 family and serves as part of an immune checkpoint (1,2). PD-L1 contains an Ig-V and Ig-C-like extracellular domain, a transmembrane domain, and a cytoplasmic tail lacking canonical signaling motifs (2,3). PD-L1 is the ligand that binds the receptor programmed-death 1 (PD-1) which is highly expressed on active T cells (1-3). PD-L1 is typically upregulated by tumor cells and antigen presenting cells (APCs), but also expressed on T cells, B cells, macrophages, dendritic cells (DC), mast cells, and some non-immune cell types (1-3). In addition to the membrane-bound, PD-L1 is released from cells both in soluble form and bound to extracellular vesicles (4).

PD-L1 binding with receptor PD-1 results in phosphorylation of in the inhibitory tyrosine-based switch motif (ITSM) domain of PD-1, which leads to recruitment of Src homology 2 domain-containing protein tyrosine-phosphatase 2 (SHP-2) and eventual downstream phosphorylation of spleen tyrosine kinase (Syk) and phospholipid inositol-3-kinase (PI3K) (1,3). Under normal conditions, the PD-L1/PD-1 signaling axis helps maintain immune tolerance and prevent destructive immune responses by inhibiting T cell activity such as proliferation, survival, cytokine production, and cytotoxic T lymphocyte (CTL) cytotoxicity (1-3). In the tumor microenvironment (TME), however, the PD-L1/PD-1 signaling axis is hijacked to promote tumor cell survival and limit anti-tumor immune response (1,3). More precisely, tumor cells can escape killing and immune surveillance due to T cell exhaustion and apoptosis (1-3).

Given the role the PD-L1/PD-1 signaling axis plays in tumor cells' ability to evade immune surveillance, it has become a target of several immunotherapeutic agents in recent years (3,5). Antibody immunotherapies that target these inhibitory checkpoint molecules has shown great promise for cancer treatment (3,5). PD-L1 and PD-1 blocking agents have been approved for treatment in a number of cancers including melanoma, non-small cell lung cancer (NSCLC), urothelial carcinoma, and Merkel-cell carcinoma (3,5). In many cancers the expression of PD-L1 in the TME has predictive value for response to blocking agents (3). Pembrolizumab, for example, is a PD-1 inhibitor that has been approved by the FDA as a second-line therapy for treatment of metastatic NSCLC in patients whose tumors express PD-L1 with a Tumor Proportion Score (TPS) greater than 1%, but also for first-line treatment in cases where patients' tumors expression PD-L1 with a TPS greater than 50%) (5). The most promising cancer immunotherapy treatments seem to point to combination therapy with both anti-cancer drugs (e.g. Gefitibin, Metformin, Etoposide) with PD-L1/PD-1 antibody blockade inhibitors (e.g. Atezolizumab, Nivolumab) (6).

References

1. Han, Y., Liu, D., & Li, L. (2020). PD-1/PD-L1 pathway: current researches in cancer. American journal of cancer research, 10(3), 727-742.

2. Jiang, Y., Chen, M., Nie, H., & Yuan, Y. (2019). PD-1 and PD-L1 in cancer immunotherapy: clinical implications and future considerations. Human vaccines & immunotherapeutics, 15(5), 1111-1122. https://doi.org/10.1080/21645515.2019.1571892

3. Sun, C., Mezzadra, R., & Schumacher, T. N. (2018). Regulation and Function of the PD-L1 Checkpoint. Immunity, 48(3), 434-452. https://doi.org/10.1016/j.immuni.2018.03.014

4. Cha, J. H., Chan, L. C., Li, C. W., Hsu, J. L., & Hung, M. C. (2019). Mechanisms Controlling PD-L1 Expression in Cancer. Molecular cell, 76(3), 359-370. https://doi.org/10.1016/j.molcel.2019.09.030

5. Tsoukalas, N., Kiakou, M., Tsapakidis, K., Tolia, M., Aravantinou-Fatorou, E., Baxevanos, P., Kyrgias, G., & Theocharis, S. (2019). PD-1 and PD-L1 as immunotherapy targets and biomarkers in non-small cell lung cancer. Journal of B.U.ON. : official journal of the Balkan Union of Oncology, 24(3), 883-888.

6. Gou, Q., Dong, C., Xu, H., Khan, B., Jin, J., Liu, Q., Shi, J., & Hou, Y. (2020). PD-L1 degradation pathway and immunotherapy for cancer. Cell death & disease, 11(11), 955. https://doi.org/10.1038/s41419-020-03140-2

Long Name

Programmed Death Ligand 1

Alternate Names

B7-H1, B7H1, CD274, PDCD1L1, PDCD1LG1, PDL1

Gene Symbol

CD274

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Product Specific Notices for PD-L1 Antibody (PDL1/8591R) [Alexa Fluor® 350]

Alexa Fluor (R) products are provided under an intellectual property license from Life Technologies Corporation. The purchase of this product conveys to the buyer the non-transferable right to use the purchased product and components of the product only in research conducted by the buyer (whether the buyer is an academic or for-profit entity). The sale of this product is expressly conditioned on the buyer not using the product or its components, or any materials made using the product or its components, in any activity to generate revenue, which may include, but is not limited to use of the product or its components: (i) in manufacturing; (ii) to provide a service, information, or data in return for payment; (iii) for therapeutic, diagnostic or prophylactic purposes; or (iv) for resale, regardless of whether they are resold for use in research. For information on purchasing a license to this product for purposes other than as described above, contact Life Technologies Corporation, 5791 Van Allen Way, Carlsbad, CA 92008 USA or outlicensing@lifetech.com. This conjugate is made on demand. Actual recovery may vary from the stated volume of this product. The volume will be greater than or equal to the unit size stated on the datasheet.

This product is for research use only and is not approved for use in humans or in clinical diagnosis. Primary Antibodies are guaranteed for 1 year from date of receipt.

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PD-L1 Antibody (PDL1/8591R) [Alexa Fluor® 350]

Novus Biologicals, part of Bio-Techne | Catalog # NBP3-24106AF350

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Background: PD-L1/B7-H1