programmed cell death 1 ligand 1; PD-L1; PDCD1 ligand 1; programmed death ligand 1; B7 homolog 1; B7-H1; CD274 (CD274, B7H1, PDCD1L1, PDCD1LG1, PDL1)
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Function
- interaction with PDCD1 inhibits T-cell proliferation by blocking cell cycle progression
Structure
- belongs to the immunoglobulin superfamily, BTN/MOG family
- contains 1 Ig-like C2-type domain
- contains 1 Ig-like V-type domain
Compartment
- single-pass type 1 membrane protein
- isoform 1: cell membrane
- isoform 2: endomembrane system
Alternative splicing
named isoforms=3
Expression
- highly expressed in the heart, skeletal muscle, placenta & lung
- weakly expressed in the thymus, spleen, kidney & liver
- expressed on activated T-cells & B-cells, dendritic cells, keratinocytes & monocytes
- up-regulated on T-cells & B-cells, dendritic cells, keratinocytes & monocytes after LPS & IFNG activation
- up-regulated in B-cells activated by surface Ig cross-linking
- expressed on some non-small-cell lung cancer (NSCLC) cells[5]
Pharmacology
- anti-CD274 antibody (nivolumab) induces tumor regression in 6-17% of patients & prolonged stabilization (24 weeks) in 12-41% of patients with advanced cancers, including:
- anti-CD274 antibody (pembrolizumab) as initial therapy for patients with NSCLC if tumor expresion of PD-L1 > 50%[5]
- atezolizumab (Tecentriq) FDA-approved to treat advanced bladder cancer
Laboratory
Comparative biology
- fecal transplantation from mice with anti-melanoma immunity augments responses to anti-PDL1 immunotherapy[4]
- augmented response apparently conferred by Bifidobacterium
More general terms
Additional terms
References
- ↑ UniProt http://www.uniprot.org/uniprot/Q9NZQ7.html
- ↑ Day CL et al, PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 2006, 443:350 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16921384
- ↑ Brahmer JR et al Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer N Engl J Med, June 2, 2012 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/22658128 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1200694
- ↑ 4.0 4.1 Sivan A, Corrales L, Hubert N et al Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science. 2015 Nov 27;350(6264):1084-9 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26541606
- ↑ 5.0 5.1 5.2 Kris MG PD-L1 Testing Should Be Standard for Every Suspected Lung Cancer. Medscape. Dec 16, 2016. http://www.medscape.com/viewarticle/873128