PD-L1 Extracellular Domain (human, recombinant)

Programmed cell death 1 ligand 1 (PD-L1), also known as B7-H1 or CD274, is a B7 family protein that is involved in regulation and attenuation of the adaptive immune response and peripheral T cell tolerance.^1,2,3,4 It is a 290-amino acid type I transmembrane protein encoded by the CD274 gene in humans and is comprised of a 239-amino acid extracellular domain consisting of a signal peptide, an IgV-like domain, and an IgC-like domain, a transmembrane domain, and a cytoplasmic tail.^1,5 PD-L1 is constitutively expressed in T and B cells, dendritic cells, macrophages, and regulatory T cells (Tregs), as well as a variety of nonhematopoietic cells and is upregulated by IFN-γ.³ Binding of PD-L1 to its receptor, programmed cell death protein 1 (PD-1), suppresses T cell proliferation, migration, and cytokine production.^2,4 PD-L1 is also aberrantly expressed in a variety of tumor cells, and expression of PD-L1 in tumor tissue is associated with poor prognosis in patients with renal cell carcinoma. ^6,7,8 Formulations containing PD-L1 blocking antibodies have been used in the treatment of a variety of cancers. Cayman's PD-L1 Extracellular Domain (human, recombinant) protein can be used for ELISA, binding assay, and cell-based assay applications. This protein is a disulfide-linked homodimer. The reduced monomer, comprised of PD-L1 (amino acids 19-239) fused to mouse IgG1 Fc at its C-terminus, consists of 455 amino acids, has a calculated molecular weight of 51.7 kDa, and a predicted N-terminus of Phe19 after signal peptide cleavage. As a result of glycosylation, the monomer migrates at approximately 66 kDa by SDS-PAGE under reducing conditions.

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1. Fabrizio, F.P., Trombetta, D., Rossi, A., et al. Gene code CD274/PD-L1: From molecular basis toward cancer immunotherapy. Ther. Adv. Med. Oncol. 10, (2018).

2. Riley, J.L. PD-1 signaling in primary T cells. Immunol. Rev. 229(1), 114-125 (2009).

3. del Rio, M.L., Buhler, L., Gibbons, C.E., et al. PD-1/PD-L1, PD-1/PD-L2, and other co-inhibitory signaling pathways in transplantation. Transpl. Int. 21(11), 1015-1028 (2008).

4. Akinleye, A., and Rasool, Z. Immune checkpoint inhibitors of PD-L1 as cancer therapeutics. J. Hematol. Oncol. 12(1), 92 (2019).

5. Keir, M.E., Butte, M.J., Freeman, G.J., et al. PD-1 and its ligands in tolerance and immunity. Annu. Rev. Immunol. 26, 677-704 (2008).

6. Ji, M., Liu, Y., Li, Q., et al. PD-1/PD-L1 pathway in non-small-cell lung cancer and its relation with EGFR mutation. J. Transl. Med. 13, 5 (2015).

7. Thompson, R.H., Dong, H., Lohse, C.M., et al. PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma. Clin. Cancer Res. 13(6), 1757-1761 (2007).

8. Thompson, R.H., Kuntz, S.M., Leibovich, B.C., et al. Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up. Cancer Res. 66(7), 3381-3385 (2006).