PD-L1 Antibody (4V8L4)

Immunohistochemistry: PD-L1 Antibody (4V8L4) [PD-L1] - Immunohistochemistry analysis of paraffin-embedded Human placenta using PD-L1 Rabbit mAb at dilution of 1:500 (40x lens). High pressure antigen retrieval performed with 0.01M Citrate Bufferr (pH 6.0) prior to IHC staining.

Immunohistochemistry: PD-L1 Antibody (4V8L4) [PD-L1] - Immunohistochemistry analysis of paraffin-embedded Human tonsil using PD-L1 Rabbit mAb at dilution of 1:500 (40x lens). High pressure antigen retrieval performed with 0.01M Citrate Bufferr (pH 6.0) prior to IHC staining.

Western Blot: PD-L1 Antibody (4V8L4) [PD-L1] - Western blot analysis of lysates from wild type (WT) and PD-L1 knockout (KO) A-549 cells using PD-L1 Rabbit mAb at 1:1000 dilution incubated overnight at 4C. Wild type (WT) and PD-L1 knockout (KO) A549 cells were treated by IFNG (100 ng/mL) at 37C for 48 hours.Secondary antibody: HRP-conjugated Goat anti-Rabbit IgG (H+L) at 1:10000 dilution.Lysates/proteins: 30 ug per lane.Blocking buffer: 3% nonfat dry milk in TBST.Detection: ECL Basic Kit .Exposure time: 45s.

Immunohistochemistry: PD-L1 Antibody (4V8L4) [PD-L1] - Immunohistochemistry analysis of paraffin-embedded Human lung adenocarcinoma using PD-L1 Rabbit mAb at dilution of 1:500 (40x lens). High pressure antigen retrieval performed with 0.01M Citrate Bufferr (pH 6.0) prior to IHC staining.

• Reactivity: Hu
• Applications: WB, IHC
• Clone: 4V8L4
• Clonality: Monoclonal
• Host: Rabbit
• Conjugate: Unconjugated

PD-L1 Antibody (4V8L4) Summary

• Additional Information: Recombinant Monoclonal Antibody
• Immunogen: Recombinant fusion protein containing a sequence corresponding to amino acids 1-290 of human PD-L1 (Q9NZQ7). MRIFAVFIFMTYWHLLNAFTVTVPKDLYVVEYGSNMTIECKFPVEKQLDLAALIVYWEMEDKNIIQFVHGEEDLKVQHSSYRQRARLLKDQLSLGNAALQITDVKLQDAGVYRCMISYGGADYKRITVKVNAPYNKINQRILVVDPVTSEHELTCQAEGYPKAEVIWTSSDHQVLSGKTTTTNSKREEKLFNVTSTLRINTTTNEIFYCTFRRLDPEENHTAELVIPELPLAHPPNERTHLVILGAILLCLGVALTFIFRLRKGRMMDVKKCGIQDTNSKKQSDTHLEET
• Isotype: IgG
• Clonality: Monoclonal
• Host: Rabbit
• Gene: CD274
• Purity: Affinity purified

Applications/Dilutions

• Dilutions:
  • Immunohistochemistry 1:100 - 1:500
  • Immunohistochemistry-Paraffin 1:100 - 1:500
  • Western Blot 1:500 - 1:1000

Packaging, Storage & Formulations

• Storage: Store at -20C. Avoid freeze-thaw cycles.
• Buffer: PBS (pH 7.3), 50% glycerol, 0.05% BSA
• Preservative: 0.05% Proclin 300
• Purity: Affinity purified

Alternate Names for PD-L1 Antibody (4V8L4)

• Avelumab
• B7-H
• B7H1
• B7-H1
• B7H1PDCD1L1
• CD274 antigenMGC142294
• CD274 molecule
• CD274
• PDCD1L1
• PDCD1LG1
• PDCD1LG1MGC142296
• PDL1
• PD-L1
• PD-L1B7 homolog 1
• PDL1PDCD1 ligand 1
• programmed cell death 1 ligand 1
• Programmed death ligand 1

Background

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

Limitations

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.

Bioinformatics

• Gene Symbol: CD274