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Protein / target

Programmed cell death 1 ligand 1

Encoded byCD274Q9NZQ7Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
5
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Structure with Ligand

Protein at a glance

Biological role

Transcription coactivator

Strongest disease association

Neoplasms

Via encoding gene CD274 · Genetic evidence · score 0.19

Therapeutic position

Established drug target

Antibodies

Research activity

Extensively researched

158 papers · latest 2025

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

Canonical identity and biological annotation from UniProt.

Function overview

Plays a critical role in induction and maintenance of immune tolerance to self.

View complete UniProt function annotation

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

Cell membraneEarly endosome membraneRecycling endosome membraneNucleusEndomembrane systemSecreted
Domains and Gene Ontology detail (35)

Domains & features

Ig-like V-typeIg-like C2-type

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

290 aa · 33 kDa · 4 isoforms

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Immune signallingUniProt · GOTranscriptional regulationUniProt · GO
View 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
View underlying pathways (7)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

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.

CD80CTLA4PDCD1HAVCR2CD28PDCD1L…ICOSSTAT3LAG3TIGITCD274

10 strongest partners — larger node and heavier line mean higher confidence

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.

Approved medicines with mapped indications

4 medicines · 10 areas

Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.

Carcinoma, Non-Small-Cell Lung3 medicines
Carcinoma, Transitional Cell2 medicines
Small Cell Lung Carcinoma2 medicines
Breast Neoplasms1 medicine
Carcinoma, Merkel Cell1 medicine
Lung Neoplasms1 medicine
Neuroendocrine Tumors1 medicine
Triple Negative Breast Neoplasms1 medicine
Urologic Neoplasms1 medicine
Broader indication categories (1)

Broad umbrella indications (e.g. “Neoplasms”). Shown here because every medicine also appears under a more specific disease above — kept for completeness, de-emphasised for clarity.

5 medicines meet Open Targets' target-level approved-medicine definition; the 4 shown here are those on this page with a canonical approved disease indication in the graph. Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

5

How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.

atezolizumab
Narrow target profileApprovedInhibitor

Programmed cell death 1 ligand 1 inhibitor

Indicated for Breast Neoplasms, Carcinoma, Non-Small-Cell Lung, Carcinoma, Transitional Cell, Lung Neoplasms

Direct interaction with this protein · Only this protein recorded as a target

durvalumab
Narrow target profileApprovedInhibitor

Programmed cell death 1 ligand 1 inhibitor

Indicated for Carcinoma, Non-Small-Cell Lung, Small Cell Lung Carcinoma, Neoplasms

Direct interaction with this protein · Only this protein recorded as a target

avelumab
Narrow target profileApprovedOther

Programmed cell death 1 ligand 1 other

Indicated for Carcinoma, Merkel Cell, Carcinoma, Transitional Cell, Neuroendocrine Tumors, Neoplasms

Direct interaction with this protein · Only this protein recorded as a target

Sugemalimab
Narrow target profileApprovedBinding agent

Programmed cell death 1 ligand 1 binding agent

Indicated for Carcinoma, Non-Small-Cell Lung, Neoplasms

Direct interaction with this protein · Only this protein recorded as a target

Adebrelimab
Narrow target profilePhase 3Inhibitor

Programmed cell death 1 ligand 1 inhibitor

Direct interaction with this protein · Only this protein recorded as a target

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.

Strongest disease associations · via encoding gene CD274

Gene-level evidence surfaced through the gene CD274that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.

Carcinoma, Non-Small-Cell Lung
0.84Well supported

Clinical evidence dominant · Open Targets 0.68

Carcinoma, Merkel Cell
0.81Well supported

Clinical evidence dominant · Open Targets 0.64

Carcinoma, Hepatocellular
0.79Well supported

Clinical evidence dominant · Open Targets 0.61

Small Cell Lung Carcinoma
0.79Well supported

Clinical evidence dominant · Open Targets 0.62

Squamous Cell Carcinoma of Head and Neck
0.78Well supported

Clinical evidence dominant · Open Targets 0.59

View evidence synthesis (5)
Carcinoma, Non-Small-Cell LungWell supported
0.84
agreement 0.730.96
Clinical61%Somatic mutation25%Literature13%RNA expression2%

Open Targets aggregate 0.68 · 4 independent evidence families

Carcinoma, Merkel CellWell supported
0.81
agreement 0.690.93
Clinical62%Somatic mutation26%Literature12%

Open Targets aggregate 0.64 · 3 independent evidence families

Carcinoma, HepatocellularWell supported
0.79
agreement 0.670.91
Clinical60%Somatic mutation27%Literature14%

Open Targets aggregate 0.61 · 3 independent evidence families

Small Cell Lung CarcinomaWell supported
0.79
agreement 0.670.91
Clinical67%Somatic mutation19%Literature14%

Open Targets aggregate 0.62 · 3 independent evidence families

Squamous Cell Carcinoma of Head and NeckWell supported
0.78
agreement 0.660.90
Clinical59%Somatic mutation28%Literature14%

Open Targets aggregate 0.59 · 3 independent evidence families

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 per-type scores above show the calculation.

Show all associations
Carcinoma, Non-Small-Cell Lung0.68
Carcinoma, Merkel Cell0.64
Small Cell Lung Carcinoma0.62
Carcinoma, Hepatocellular0.61
Squamous Cell Carcinoma of Head and Neck0.59
Neoplasms0.59
Urothelial carcinoma0.59
Breast Neoplasms0.55
Lung Neoplasms0.52
Esophageal Squamous Cell Carcinoma0.48

Drug development

13 compounds recorded · 5 approved · 8 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 5 drugs that target this protein in Forefront's canonical graph (4 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (10)
ATEZOLIZUMABApproval
ENVAFOLIMABPhase 3
BINTRAFUSP ALFAPhase 3
SUGEMALIMABApproval
ADEBRELIMABPhase 3
AVELUMABApproval
DANBURSTOTUGPhase 2
PACMILIMABPhase 2
DURVALUMABApproval
SOCAZOLIMABPhase 3

Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.

Tractability

Small moleculesEmerging

Feasibility evidence (structure with ligand and high-quality ligand) — no clinical-stage drug of this modality recorded.

AntibodiesStrong

Approved Drug and UniProt loc high conf support this modality.

Protein degradersEmerging

Feasibility evidence (literature and uniprot ubiquitination) — no clinical-stage drug of this modality recorded.

Other modalitiesStrong

Advanced Clinical support this modality.

View underlying tractability evidence (11)
SM · Structure with LigandSM · High-Quality LigandSM · Med-Quality PocketAB · Approved DrugAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMMPR · LiteraturePR · UniProt UbiquitinationPR · Small Molecule BinderOC · Advanced Clinical

Raw Open Targets tractability assessment buckets, by modality.

Clinical trials

30

Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.

View all trials (26)

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 4 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.

  1. Trial status changed2026-08-25

    Phase I/II Study of Neoadjuvant Inhaled Azacytidine With Platinum-Based Chemotherapy and Durvalumab (MEDI4736) - a Combined Epigenetic-Immunotherapy (AZA-AEGEAN) Regimen for Operable Early-Stage Non-Small Cell Lung Cancer (NSCLC)

    Status changed to Suspended · ClinicalTrials.gov · via durvalumab

  2. Trial results posted2026-08-07

    A Safety Run-In and Phase II Study Evaluating the Efficacy, Safety, and Impact on the Tumor Microenvironment of the Combination of Tocilizumab, Atezolizumab, and Fractionated Stereotactic Radiotherapy in Recurrent Glioblastoma

    Results posted · ClinicalTrials.gov · via atezolizumab

  3. Trial status changed2026-07-27

    A Phase IIIb Study of Durvalumab as Consolidation Treatment for Patients Diagnosed With Limited Stage Small Cell Lung Cancer Who Have Not Progressed Following Definitive Concurrent or Sequential Platinum-based Chemoradiation Therapy in Spain (ALBORAN).

    Status changed to Active, not recruiting · ClinicalTrials.gov · via durvalumab

  4. Trial results posted2026-07-22

    A Phase II Trial of Atezolizumab Plus Induction Chemotherapy (CT) Plus Chemo-radiotherapy and Atezolizumab Maintenance Therapy in Non-resectable Stage IIIA-IIIB Non-small Cell Lung Cancer (NSCLC) Patients

    Results posted · ClinicalTrials.gov · via atezolizumab

  5. New publication2025-08-01
    Early ctDNA and Survival in Metastatic Colorectal Cancer Treated With Immune Checkpoint Inhibitors: A Secondary Analysis of the SAMCO-PRODIGE 54 Randomized Clinical Trial.

    JAMA oncology · 2025 · 9 citations · Europe PMC · via avelumab

  6. New publication2025-01-06
    Autogene cevumeran with or without atezolizumab in advanced solid tumors: a phase 1 trial.

    Nature medicine · 2025 · 66 citations · Europe PMC · via atezolizumab

  7. New publication2024-08-01
    Plasma versus Tissue Tumor Mutational Burden as Biomarkers of Durvalumab plus Tremelimumab Response in Patients with Metastatic Colorectal Cancer in the CO.26 Trial.

    Clinical cancer research : an official journal of the American Association for Cancer Research · 2024 · 15 citations · Europe PMC · via durvalumab

  8. Regulatory approval2024-07-24

    Approval: Cejemly (EMA)

    ema · regulatory · ema · via Sugemalimab

  9. New publication2024-03-29
    CONTACT-01: A Randomized Phase III Trial of Atezolizumab + Cabozantinib Versus Docetaxel for Metastatic Non-Small Cell Lung Cancer After a Checkpoint Inhibitor and Chemotherapy.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024 · 48 citations · Europe PMC · via atezolizumab

  10. Regulatory approval2018-09-21

    Approval: Imfinzi (EMA)

    ema · regulatory · ema · via durvalumab

  11. Regulatory approval2017-09-20

    Approval: Tecentriq (EMA)

    ema · regulatory · ema · via atezolizumab

  12. Regulatory approval2017-09-18

    Approval: Bavencio (EMA)

    ema · regulatory · ema · via avelumab

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.

Research activity

158 papers · to 2025

Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.

Most cited

Borghaei H · The New England journal of medicine · 2015

Keir ME · Annual review of immunology · 2008

Ferris RL · The New England journal of medicine · 2016

Socinski MA · The New England journal of medicine · 2018

Ayers M · The Journal of clinical investigation · 2017

Recent

Europe PMC papers linked directly to this protein.