Protein / target

Cytotoxic T-lymphocyte protein 4

CTLA4P16410Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
2
Approved medicines
30
Clinical trials
Small-molecule tractable
Druggability
Structure with Ligand

Protein at a glance

Biological role

Receptor decoy activity

Primary system

Immune system

Strongest disease association

hypothyroidism

Genetic evidence · score 0.96

Therapeutic maturity

Clinically validated target

2 approved medicines against this target

Druggability

Small molecule

Open Targets tractability · Structure with Ligand

Clinical development

2 approved · 4 in clinical development

30 linked trials

Research activity

Actively researched

56 papers · latest 2026

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

Inhibitory receptor acting as a major negative regulator of T-cell responses (PubMed:11279501, PubMed:11279502, PubMed:16551244, PubMed:1714933, PubMed:18641304, PubMed:28484017). Acts as a decoy receptor: the affinity of CTLA4 for its natural B7 family ligands, CD80 and CD86, is considerably stronger than the affinity of their cognate stimulatory coreceptor CD28 (PubMed:11279501, PubMed:11279502, PubMed:16551244, PubMed:1714933, PubMed:28484017)

Subcellular location

Cell membrane
Domains and Gene Ontology detail (19)

Domains & features

Ig-like V-type

Gene Ontology

  • Cclathrin-coated endocytic vesicle
  • Cexternal side of plasma membrane
  • CGolgi apparatus
  • Cperinuclear region of cytoplasm
  • Cplasma membrane
  • Cprotein complex involved in cell adhesion
  • Freceptor decoy activity
  • Padaptive immune response
  • PB cell receptor signaling pathway
  • PDNA damage response
  • Pimmune response
  • Pnegative regulation of B cell proliferation

223 aa · 25 kDa · 5 isoforms

Biological roles

Reactome v97

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

Immune signallingGOCell adhesionGOApoptosis & cell deathGO
View supporting evidence

Immune signalling

  • ·adaptive immune response
  • ·B cell receptor signaling pathway
  • ·immune response
  • ·negative regulation of B cell proliferation

Cell adhesion

  • ·protein complex involved in cell adhesion

Apoptosis & cell death

  • ·positive regulation of apoptotic process
View underlying pathways (3)

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.

CD86LOC102…CD80CD274ICOSPDCD1L…PDCD1ICOSLGLGALS9CD28CTLA4

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.

Drugs targeting this protein

1

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.

tremelimumab
Narrow target profileApprovedInhibitor

Cytotoxic T-lymphocyte protein 4 inhibitor

Appears in clinical studies involving non-small cell lung carcinoma, hepatocellular carcinoma, non-small cell lung carcinoma, hepatocellular carcinoma

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

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

Translational evidence

Open Targets 26

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.

hypothyroidism0.96

Genetic · overall 0.59

rheumatoid arthritis0.94

Genetic · overall 0.60

Graves disease0.93

Genetic · overall 0.58

type 1 diabetes mellitus0.92

Genetic · overall 0.59

Hashimoto thyroiditis0.87

Genetic · overall 0.67

Highest-confidence therapeutic associations

Diseases where a drug acting on this target has already reached clinical development.

melanoma0.96

Clinical · overall 0.61

non-small cell lung carcinoma0.96

Clinical · overall 0.61

hepatocellular carcinoma0.95

Clinical · overall 0.61

Highest overall evidence

Remaining associations by Open Targets' aggregated evidence score.

autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency0.80

Genetic

systemic lupus erythematosus0.62

Literature

Show all associations
autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency0.80
Hashimoto thyroiditis0.67
systemic lupus erythematosus0.62
melanoma0.61
non-small cell lung carcinoma0.61
hepatocellular carcinoma0.61
rheumatoid arthritis0.60
hypothyroidism0.59
type 1 diabetes mellitus0.59
Graves disease0.58

Open Targets ranks 1,709 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 · 6 total

QUAVONLIMABPhase 3

clear cell renal carcinoma · non-small cell lung carcinoma · hepatocellular carcinoma

ZALIFRELIMABPhase 2

non-small cell lung carcinoma · cervical cancer · soft tissue sarcoma

CADONILIMABPhase 3

cervical cancer · gastroesophageal junction adenocarcinoma · gastric adenocarcinoma

ERFONRILIMABPhase 3

non-small cell lung carcinoma · non-small cell lung carcinoma · pancreatic ductal adenocarcinoma

IPILIMUMABApproval

metastatic melanoma · melanoma · colorectal neoplasm

TREMELIMUMABApproval

non-small cell lung carcinoma · hepatocellular carcinoma · non-small cell lung carcinoma

Tractability

SM · Structure with LigandAB · Approved DrugAB · UniProt loc high confAB · GO CC high confAB · UniProt SigP or TMHMM

Safety liabilities

a hypersensitivity reactiongingival overgrowthlater onset of bortezomib-induced peripheral neuropathyearlier onset of bortezomib-induced peripheral neuropathyparadoxical psoriasiform reactions

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.

Show remaining trials (24)

ClinicalTrials.gov via the drug-target graph.

Research activity

56 papers · to 2026

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

Most cited

Recent

Immune checkpoint inhibition perturbs neuro-immune homeostasis and impairs cognitive function.

Ifejeokwu OV · Journal of experimental & clinical cancer research : CR · 2025

Hypoxia is linked to acquired resistance to immune checkpoint inhibitors in lung cancer.

Robles-Oteíza C · The Journal of experimental medicine · 2025

Soluble CTLA-4 attenuates T cell activation and modulates anti-tumor immunity.

Kennedy PT · Molecular therapy : the journal of the American Society of Gene Therapy · 2024

Europe PMC papers linked directly to this protein.

Forefront confidence

Synthesis

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.

hypothyroidismWell supported
0.96
agreement 0.821.00
Genetic96%Literature4%

Open Targets aggregate 0.59 · 2 independent evidence families

rheumatoid arthritisWell supported
0.95
agreement 0.811.00
Genetic87%Literature13%

Open Targets aggregate 0.60 · 2 independent evidence families

Graves diseaseWell supported
0.94
agreement 0.801.00
Genetic94%Literature6%

Open Targets aggregate 0.58 · 2 independent evidence families

type 1 diabetes mellitusWell supported
0.93
agreement 0.791.00
Genetic87%Literature13%

Open Targets aggregate 0.59 · 2 independent evidence families

autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiencyWell supported
0.89
agreement 0.771.00
Genetic81%Animal model17%Literature2%Genetic literaturedup

Open Targets aggregate 0.80 · 3 independent evidence families · 1 not counted as duplicate

This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. 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

10

Recent activity around this target, drawn from one canonical event stream. Every item is reached through a drug that targets this protein, so each event is news about that drug rather than about the protein directly.

  1. Industry development2026-04-02
    Another AstraZeneca Emerald glimmers as Imfinzi, Imjudo delay liver cancer progression

    Fierce Pharma · news · via tremelimumab

  2. 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 tremelimumab

  3. Regulatory approval2023-02-20

    Approval: Imjudo (EMA)

    ema · regulatory · ema · via tremelimumab

  4. New publication2022-11-03
    Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study.

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023 · 340 citations · Europe PMC · via tremelimumab

  5. New publication2022-06-06
    Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma.

    NEJM evidence · 2022 · 1,149 citations · Europe PMC · via tremelimumab

  6. New publication2020-06-01
    Effect of Combined Immune Checkpoint Inhibition vs Best Supportive Care Alone in Patients With Advanced Colorectal Cancer: The Canadian Cancer Trials Group CO.26 Study.

    JAMA oncology · 2020 · 307 citations · Europe PMC · via tremelimumab

  7. New publication2020-05-01
    Durvalumab With or Without Tremelimumab vs Standard Chemotherapy in First-line Treatment of Metastatic Non-Small Cell Lung Cancer: The MYSTIC Phase 3 Randomized Clinical Trial.

    JAMA oncology · 2020 · 499 citations · Europe PMC · via tremelimumab

  8. New publication2020-04-12
    Durvalumab with or without tremelimumab in patients with recurrent or metastatic head and neck squamous cell carcinoma: EAGLE, a randomized, open-label phase III study.

    Annals of oncology : official journal of the European Society for Medical Oncology · 2020 · 291 citations · Europe PMC · via tremelimumab

  9. New publication2019-03-10
    Tremelimumab in Combination With Microwave Ablation in Patients With Refractory Biliary Tract Cancer.

    Hepatology (Baltimore, Md.) · 2019 · 78 citations · Europe PMC · via tremelimumab

  10. New publication2016-11-02
    Tremelimumab in combination with ablation in patients with advanced hepatocellular carcinoma.

    Journal of hepatology · 2017 · 631 citations · Europe PMC · via tremelimumab

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.