Protein / target
Programmed cell death 1 ligand 1
Protein at a glance
Biological role
Transcription coactivator activity
Primary system
Immune system
Strongest disease association
neoplasm
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
5 approved · 8 in clinical development
Research activity
Extensively researched
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:31399419). As a ligand for the inhibitory receptor PDCD1/PD-1, modulates the activation threshold of T-cells and limits T-cell effector response (PubMed:11015443, PubMed:28813410, PubMed:28813417, PubMed:36727298). Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10) (PubMed:10581077). Can also act as a transcription coactivator: in response to hypoxia, translocates into the nucleus via its interaction with phosphorylated STAT3 and promotes transcription of GSDMC, leading to pyroptosis (PubMed:32929201)
Subcellular location
Domains and Gene Ontology detail (35)Hide
Domains & features
Gene Ontology
- Ccytosol
- Cearly endosome membrane
- Cendoplasmic reticulum membrane
- Cexternal side of plasma membrane
- Cextracellular exosome
- CGolgi membrane
- Cnuclear speck
- Cnucleoplasm
- Cplasma membrane
- Crecycling endosome membrane
- Freceptor ligand activity
- Ftranscription coactivator activity
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Immune signalling
- ·Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:1…
- ·adaptive immune response
- ·immune response
- ·negative regulation of activated T cell proliferation
Transcriptional regulation
- ·Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:1…
- ·transcription coactivator activity
Apoptosis & cell death
- ·positive regulation of activated CD8-positive, alpha-beta T cell apoptotic process
View underlying pathways (7)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
Programmed cell death 1 ligand 1 inhibitor
Appears in clinical studies involving lung cancer, urothelial carcinoma, non-small cell lung carcinoma, breast cancer
Programmed cell death 1 ligand 1 inhibitor
Appears in clinical studies involving non-small cell lung carcinoma, small cell lung carcinoma, urothelial carcinoma, non-small cell lung carcinoma
Programmed cell death 1 ligand 1 other
Appears in clinical studies involving Merkel cell skin cancer, Merkel cell skin cancer, urothelial carcinoma, neuroendocrine neoplasm
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Strongest genetic associations
Human genetic evidence — the most direct causal link between this target and a disease.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 1,982 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 13 total
lung cancer · urothelial carcinoma · non-small cell lung carcinoma
biliary tract cancer · rectum adenocarcinoma · non-small cell lung carcinoma
non-small cell lung carcinoma · biliary tract cancer · non-small cell lung carcinoma
non-small cell lung carcinoma · non-small cell lung carcinoma · neoplasm
small cell lung carcinoma · non-small cell lung carcinoma · colorectal cancer
Merkel cell skin cancer · Merkel cell skin cancer · urothelial carcinoma
biliary tract cancer · diffuse large B-cell lymphoma · mature T-cell and NK-cell non-Hodgkin lymphoma
medulloblastoma · neoplasm · breast cancer
non-small cell lung carcinoma · small cell lung carcinoma · urothelial carcinoma
small cell lung carcinoma · cervical cancer · urothelial carcinoma
Tractability
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Research activity
Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.
Most cited
Recent
Europe PMC papers linked directly to this protein.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 3 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Industry developmentAnother AstraZeneca Emerald glimmers as Imfinzi, Imjudo delay liver cancer progression
- New publicationModulation of fibronectin extracellular matrix enhances anti-tumor efficacy of immune checkpoint blockade.
- New publicationEarly ctDNA and Survival in Metastatic Colorectal Cancer Treated With Immune Checkpoint Inhibitors: A Secondary Analysis of the SAMCO-PRODIGE 54 Randomized Clinical Trial.
- New publicationAutogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.
- New publicationPlasma versus Tissue Tumor Mutational Burden as Biomarkers of Durvalumab plus Tremelimumab Response in Patients with Metastatic Colorectal Cancer in the CO.26 Trial.
- New publicationCONTACT-01: A Randomized Phase III Trial of Atezolizumab + Cabozantinib Versus Docetaxel for Metastatic Non-Small Cell Lung Cancer After a Checkpoint Inhibitor and Chemotherapy.
- New publicationBiomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial.
- New publicationPhase 1/2 study of monalizumab plus durvalumab in patients with advanced solid tumors.
- New publicationAtezolizumab in Combination With Carboplatin and Survival Outcomes in Patients With Metastatic Triple-Negative Breast Cancer: The TBCRC 043 Phase 2 Randomized Clinical Trial.
- New publicationFirst-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer: Clinical and Biomarker Results.
- New publicationAnti-TIGIT Antibody Tiragolumab Alone or With Atezolizumab in Patients With Advanced Solid Tumors: A Phase 1a/1b Nonrandomized Controlled Trial.
- New publicationNeoadjuvant Durvalumab Alone or Combined with Novel Immuno-Oncology Agents in Resectable Lung Cancer: The Phase II NeoCOAST Platform Trial.
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.