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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)

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: a) non-small-cell lung cancer (NSCLC) b) cutaneous melanoma c) renal-cell carcinoma - 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: - PD-L1 in tissue Comparative biology: - fecal transplantation from mice with anti-melanoma immunity augments responses to anti-PDL1 immunotherapy [4] - augmented response apparently conferred by Bifidobacterium

Interactions

molecular events

Related

apoptosis atezolizumab (Tecentriq) PD-L1 in blood PD-L1 in specimen PD-L1 in tissue

General

cluster-of-differentiation antigen; cluster designation antigen; CD antigen glycoprotein

Properties

SIZE: MW = 33 kD entity length = 290 aa COMPARTMENT: cellular membrane MOTIF: signal sequence {1-18} immunoglobulin superfamily domain {19-127} MOTIF: N-glycosylation site {N35} cysteine residue {C40} MODIFICATION: cysteine residue {C114} cysteine residue {C114} MODIFICATION: cysteine residue {C40} immunoglobulin superfamily domain {133-225} MOTIF: cysteine residue {C155} MODIFICATION: cysteine residue {C209} N-glycosylation site {N192} N-glycosylation site {N200} cysteine residue {C209} MODIFICATION: cysteine residue {C155} N-glycosylation site {N219} transmembrane domain {239-259}

Database Correlations

OMIM 605402 UniProt Q9NZQ7 PFAM correlations Entrez Gene 29126 Kegg hsa:29126

References

  1. UniProt :accession Q9NZQ7
  2. 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: 16921384
  3. Brahmer JR et al Safety and Activity of Anti-PD-L1 Antibody in Patients with Advanced Cancer N Engl J Med, June 2, 2012 PMID: 22658128 http://www.nejm.org/doi/full/10.1056/NEJMoa1200694
  4. 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: 26541606
  5. Kris MG PD-L1 Testing Should Be Standard for Every Suspected Lung Cancer. Medscape. Dec 16, 2016. http://www.medscape.com/viewarticle/873128