PD-L1
PD-L1 is the tumour's side of the PD-1 brake, and also the biomarker that decides who gets immunotherapy. This dossier gathers the 5 products (4 approved), 33 trials, 4 pathways and 5 resistance routes in the corpus that involve it, with external identifiers so it can be joined to UniProt, ChEMBL, Open Targets and the rest of biology.
5
products
33
trials
5
cancers with prevalence
4
pathways
5
resistance routes
0
hotspots
1
open questions
8
key papers
Biology
Expressed on tumour and immune cells; induced by interferon-gamma.
Where it is found
- Tumour cells and immune cells across most cancers
Cancers
Anal cancer (squamous cell carcinoma)Biliary tract cancer (cholangiocarcinoma)Bladder & urothelial cancerCervical cancerCutaneous squamous cell carcinomaEndometrial cancerGastric & gastro-oesophageal junction cancerGestational trophoblastic neoplasiaHead and neck squamous cell carcinomaHepatocellular carcinomaHodgkin lymphomaMerkel cell carcinomaMesotheliomaNasopharyngeal carcinomaNon-small-cell lung cancerOesophageal cancerOvarian cancerSmall-cell lung cancerTriple-negative breast cancer (TNBC)
Technologies aimed at it
Elsewhere: identifiers and databases
Built from HGNC, Ensembl, UniProt and ChEMBL idsHow common it is, by cancer
Full matrix →| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Head and neck squamous cell carcinoma | 80-85% | CPS >=1 | KEYNOTE-048 | Wikipedia |
| Triple-negative breast cancer | 35-40% | CPS >=10 (22C3), metastatic | KEYNOTE-355 screening | Wikipedia |
| Non-small-cell lung cancer | 25-30% | TPS >=50% | ~60-65% TPS >=1% | Wikipedia |
| Bladder & urothelial cancer | 25-30% | CPS >=10 | Wikipedia | |
| Small-cell lung cancer | 15-20% | Any tumour-cell expression | Wikipedia |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Products by modality and phase
Browse products →| Modality | Approved | Withdrawn or failed |
|---|---|---|
| Antibody 4 | ||
| Imaging agent 1 | — |
Trials
Evidence ranking →| Trial | Phase | Status | Setting | Result | Products |
|---|---|---|---|---|---|
| DREAM3R NCT04334759 | 3 | Negative | Unresectable pleural mesothelioma, first line: durvalumab + platinum-pemetrexed vs chemotherapy | Stopped early; primary endpoint not met. | |
| EMERALD-3 NCT05301842 | 3 | Positive | Embolisation-eligible unresectable HCC: STRIDE (durvalumab + tremelimumab) + lenvatinib + TACE vs TACE | PFS HR ~0.70 (interim); OS immature. | |
| ATOMIC (Alliance A021502) NCT02912559 | 3 | Positive | Resected stage III dMMR colon cancer: adjuvant FOLFOX + atezolizumab (12 months) vs FOLFOX | 3-year DFS 86.4% vs 76.6%, HR 0.50. | |
| IMforte NCT05091567 | 3 | Positive | First-line maintenance after induction chemo-immunotherapy in ES-SCLC: lurbinectedin + atezolizumab vs atezolizumab | OS 13.2 vs 10.6 months (HR 0.73); PFS HR 0.54. | |
| IMvigor011 NCT04660344 | 3 | Positive | Muscle-invasive bladder cancer after cystectomy, ctDNA-positive (Signatera): atezolizumab vs placebo | DFS HR 0.64; OS HR 0.59 in ctDNA+. | |
| KEYNOTE-B96 / ENGOT-ov65 NCT05116189 | 3 | Positive | Platinum-resistant recurrent ovarian cancer, 1-2 prior lines: pembrolizumab + weekly paclitaxel ± bevacizumab vs placebo + paclitaxel ± bevacizumab | OS 18.2 vs 14.0 months in CPS ≥1 (HR 0.76); ITT OS HR 0.82. | |
| MATTERHORN NCT04592913 | 3 | Positive | Resectable stage II-IVA gastric/GEJ adenocarcinoma: perioperative FLOT + durvalumab vs FLOT + placebo | EFS HR 0.71; OS HR 0.78; 3-year OS 68.6%. | |
| POTOMAC NCT03528694 | 3 | Positive | BCG-naive high-risk non-muscle-invasive bladder cancer: durvalumab + BCG (induction and maintenance) vs BCG | DFS HR 0.68. | |
| ADRIATIC NCT03703297 | 3 | Positive | Limited-stage SCLC without progression after concurrent chemoradiotherapy: durvalumab consolidation (up to 2 years) vs placebo | OS 55.9 vs 33.4 months, HR 0.73. | |
| BEAT-meso (ETOP 13-18) NCT03762018 | 3 | Mixed | Advanced pleural mesothelioma, first line: bevacizumab + carboplatin-pemetrexed ± atezolizumab | OS not significantly improved overall; benefit in non-epithelioid subgroup. | |
| EMERALD-1 NCT03778957 | 3 | Mixed | Embolisation-eligible unresectable HCC: TACE + durvalumab ± bevacizumab vs TACE + placebo | PFS HR 0.77; OS HR 0.80, not significant. | |
| NIAGARA NCT03732677 | 3 | Positive | Cisplatin-eligible muscle-invasive bladder cancer: neoadjuvant durvalumab + gemcitabine-cisplatin, cystectomy, adjuvant durvalumab vs neoadjuvant chemotherapy and cystectomy | EFS HR 0.68; OS HR 0.75. | |
| BEATcc / ENGOT-Cx10 / GOG-3030 NCT03556839 | 3 | Positive | Metastatic, persistent, or recurrent cervical cancer, first line: atezolizumab + cisplatin/carboplatin-paclitaxel + bevacizumab vs the same without atezolizumab | OS 32.1 vs 22.8 months (HR 0.68). | |
| CONTACT-03 NCT04338269 | 3 | Negative | Advanced RCC progressing on or after a PD-1/PD-L1 inhibitor: atezolizumab + cabozantinib vs cabozantinib | PFS HR 1.03; OS HR 0.94, negative. | |
| DUO-E / GOG-3041 / ENGOT-EN10 NCT04269200 | 3 | Positive | Newly diagnosed advanced or recurrent endometrial cancer: chemotherapy + durvalumab, then durvalumab ± olaparib maintenance, vs chemotherapy | PFS HR 0.42 (dMMR, durvalumab); 0.57 (pMMR, durvalumab + olaparib). | |
| DUO-O / ENGOT-ov46 NCT03737643 | 3 | Mixed | Newly diagnosed non-BRCA-mutated advanced ovarian cancer: chemotherapy + bevacizumab + durvalumab, then durvalumab + bevacizumab ± olaparib maintenance, vs standard | PFS HR 0.63; interim OS HR 0.95. | |
| IMbrave050 NCT04102098 | 3 | Negative | Adjuvant atezolizumab + bevacizumab vs active surveillance after resection or ablation of high-risk HCC | Interim RFS HR 0.72; benefit not sustained at update. | |
| HIMALAYA NCT03298451 | 3 | Positive | First-line unresectable HCC: STRIDE (single priming dose tremelimumab + durvalumab) vs sorafenib | OS HR 0.78; 5-year OS 19.6% vs 9.4%. | |
| TOPAZ-1 NCT03875235 | 3 | Positive | First-line advanced biliary tract cancer: gemcitabine-cisplatin + durvalumab vs + placebo | OS HR 0.76; 2-year OS 23.6% vs 11.5%. | |
| CheckMate 649 NCT02872116 | 3 | Positive | First-line HER2-negative advanced gastric/GEJ/oesophageal adenocarcinoma: nivolumab + chemotherapy vs chemotherapy | CPS ≥5: OS 14.4 vs 11.1 months (HR 0.71); 5-year OS 16% vs 6%. | |
| IMbrave150 NCT03434379 | 3 | Positive | First-line unresectable HCC: atezolizumab + bevacizumab vs sorafenib | OS 19.2 vs 13.4 months, HR 0.66. | |
| IMpassion131 NCT03125902 | 3 | Negative | First-line metastatic TNBC: atezolizumab + paclitaxel vs paclitaxel | PFS HR 0.82 (not significant); OS trend unfavourable; US indication withdrawn 2021. | |
| JAVELIN Bladder 100 NCT02603432 | 3 | Positive | Advanced urothelial cancer without progression after 4-6 cycles of platinum chemotherapy: avelumab maintenance + best supportive care vs BSC | OS 21.4 vs 14.3 months, HR 0.69. | |
| JAVELIN Head and Neck 100 NCT02952586 | 3 | Negative | Locally advanced HNSCC: avelumab + chemoradiation then avelumab maintenance vs chemoradiation | PFS HR 1.21; futility. | |
| CASPIAN NCT03043872 | 3 | Positive | First-line extensive-stage SCLC: platinum-etoposide + durvalumab (± tremelimumab) vs platinum-etoposide | OS 13.0 vs 10.3 months, HR 0.73; 3-year OS 17.6% vs 5.8%. | |
| KEYNOTE-048 NCT02358031 | 3 | Positive | Untreated recurrent or metastatic HNSCC: pembrolizumab alone, pembrolizumab + platinum/5-FU, or cetuximab + platinum/5-FU (EXTREME) | OS 14.9 vs 10.7 months (CPS ≥20, monotherapy); 13.0 vs 10.7 (all, with chemotherapy). | |
| IMpassion130 NCT02425891 | 3 | Mixed | First-line metastatic TNBC: atezolizumab + nab-paclitaxel | PFS HR 0.62 in PD-L1+; approval withdrawn 2021 (US). | |
| IMpower133 NCT02763579 | 3 | Positive | First-line extensive-stage SCLC: carboplatin-etoposide + atezolizumab vs carboplatin-etoposide + placebo | OS 12.3 vs 10.3 months, HR 0.70. | |
| PACIFIC NCT02125461 | 3 | Positive | Unresectable stage III NSCLC without progression after chemoradiation: durvalumab 1 year vs placebo | OS HR 0.68; 5-year OS 42.9% vs 33.4%. | |
| KEYNOTE-024 & KEYNOTE-189 NCT02142738 | 3 | Positive | First-line metastatic NSCLC without EGFR/ALK: pembrolizumab alone (PD-L1 TPS ≥50%, KEYNOTE-024) or pembrolizumab + platinum-pemetrexed (any PD-L1, non-squamous, KEYNOTE-189) | 5-year OS 31.9% vs 16.3% (024); 19.4% vs 11.3% (189). | |
| DeLLphi-305 NCT06211036 | 3 | Recruiting | First-line maintenance in ES-SCLC after platinum-etoposide-durvalumab: tarlatamab + durvalumab vs durvalumab | ||
| TROPION-Breast03 NCT05629585 | 3 | Active | Stage I–III TNBC with residual invasive disease after neoadjuvant therapy: adjuvant Dato-DXd ± durvalumab vs investigator's choice (capecitabine, pembrolizumab, or both) | ||
| TROPION-Breast05 NCT06103864 | 3 | Recruiting | First-line PD-L1+ metastatic TNBC: Dato-DXd ± durvalumab vs pembrolizumab + chemotherapy |
Resistance routes that involve this target
Unaddressed routes → Immune evasion · PD-1 / PD-L1 checkpoint inhibitors
Loss of antigen presentation (B2M, HLA, JAK1/2)
Frequency: Acquired resistance in melanoma: ~25% JAK/B2M
Mutations in B2M or HLA class I stop tumour cells displaying antigen; JAK1/2 loss removes interferon responsiveness (and PD-L1 induction).
Countermeasures · 1
- NK-cell and CAR-based approaches that do not need MHC; T-cell engagers
Immune evasion · PD-1 / PD-L1 checkpoint inhibitors
Immune-desert / excluded tumours
No pre-existing T-cell infiltrate (cold tumour) or T cells held at the margin by TGF-β and stroma.
Countermeasures · 3
- Radiation, oncolytic viruses, ADC + IO to prime
- Personalised neoantigen vaccines to supply T cells
- TIL therapy after PD-1 failure
Bypass · PD-1 / PD-L1 checkpoint inhibitors
Alternative checkpoints (LAG-3, TIM-3, TIGIT)
Exhausted T cells co-express other inhibitory receptors.
Countermeasures · 1
- Relatlimab + nivolumab (LAG-3) works; TIGIT combinations failed
Immune evasion · PD-1 / PD-L1 checkpoint inhibitors
Immunosuppressive myeloid cells and VEGF
MDSCs, M2 macrophages, and VEGF suppress T-cell function and dendritic-cell maturation.
Countermeasures · 1
- PD-1 + VEGF blockade; PD-1×VEGF bispecifics
Antigen loss · PD-1 / PD-L1 checkpoint inhibitors
Loss of neoantigens / low TMB
Immunoediting removes the clones that carried immunogenic mutations.
Countermeasures · 1
- Vaccines against shared antigens (KRAS)
Pathways where it is a node
Pathway-to-drug matrix →- Antigen presentation & immune editingNode: PD-L1 induction · 2 druggable nodes
How the immune system sees cancer, and how cancer learns to hide. Tumours display fragments of their proteins on MHC molecules; T cells kill the ones they recognise; the survivors are the ones that stopped showing fragments or switched on brakes.
Which nodes have drugs → - JAK–STAT signallingNode: MHC-I, PD-L1 (STAT1) · 1 druggable nodes
The relay that turns cytokine signals into gene changes. Overactive in blood cancers (JAK2 in myelofibrosis), it is also the wire that carries interferon's cancer-killing message, so tumours cut it to escape immunotherapy.
Which nodes have drugs → - Myeloid suppression: TAMs, MDSCs & don't-eat-me signalsNode: IL-10, TGF-β, PD-L1 · 4 druggable nodes
Tumours recruit the body's clean-up cells (macrophages and immature myeloid cells) and re-train them as bodyguards. They switch off T cells, build vessels, and, when a therapeutic antibody flags a cancer cell for eating, are told 'don't eat me' by CD47 on its surface.
Which nodes have drugs → - PD-1 / PD-L1 immune checkpoint & T-cell activationNode: PD-L1 on tumour · 4 druggable nodes
How T cells decide to attack. A T cell needs to see the target (TCR-MHC) and get a 'go' signal (CD28). PD-1 and CTLA-4 are 'stop' signals; tumours exploit them. Checkpoint inhibitors remove the stop.
Which nodes have drugs →
Companion diagnostics and assays
Assay registry →| Assay | Platform | Cut-off | Gates |
|---|---|---|---|
| PD-L1 IHC 22C3 pharmDx Agilent (Dako) · FDA CDx 2015 | IHC | TPS at least 1% or at least 50% (NSCLC); CPS at least 1 (head and neck, oesophageal, gastric); CPS at least 10 (TNBC, gastric first line); CPS at least 1 (cervical) | |
| VENTANA PD-L1 (SP142) Assay Roche Diagnostics · FDA CDx 2016 | IHC | IC at least 5% (urothelial, historic); IC at least 1% (TNBC, indication later withdrawn); TC at least 50% or IC at least 10% (NSCLC) | |
| VENTANA PD-L1 (SP263) Assay Roche Diagnostics · FDA CDx | IHC | TC at least 1% (durvalumab after chemoradiotherapy, NSCLC; PACIFIC-derived) | |
| PD-L1 IHC 28-8 pharmDx Agilent (Dako) · FDA CDx 2020 | IHC | TC at least 1% (nivolumab plus ipilimumab, first-line NSCLC) | |
| Signatera (tumour-informed ctDNA MRD) Natera · Breakthrough device | NGS plasma | Two or more variants detected above the assay threshold defines ctDNA-positive (IMvigor011: adjuvant atezolizumab for ctDNA-positive bladder cancer) |
Preclinical models
All models →No model entry for this target yet; check the cancer entries on the models page.
Open questions
All open questions →- 01
Can PD-L1 scoring be harmonised across antibodies (22C3, SP263, 28-8, SP142) and cut-points (TPS, CPS, IC) so one test serves every drug?
implementationregulatorWhy unresolved. Each drug was approved with its own assay and threshold; concordance is good for tumour-cell scoring but poor for immune-cell and combined scores, so patients are classified differently by which kit the lab bought.
What would answer it. Cross-assay concordance studies tied to outcomes, digital calibration standards, and labels that accept validated equivalent assays.
Source: KEYNOTE-189, NEJM 2018
Ideas and companies
Ideas that involve this target · 6
Anchor a TGF-beta trap in the tumour stroma so it cannot act everywhereExtended-interval immunotherapy: give checkpoint inhibitors every 8-12 weeks once stableLock the biomarker cut-off before phase 3, and publish itOne digital PD-L1 scale that maps across all the competing assaysRandomised trials of stopping immunotherapy after one year versus continuingRandomised trials to test whether biomarker-negative patients really do not benefit
Companies with products against it · 3
Key papers and the live literature
Preprints →- IMvigor011: using a blood test for leftover cancer to decide who gets immunotherapy after bladder surgery · New England Journal of Medicine 2025
- ADRIATIC: durvalumab after chemoradiotherapy for limited-stage small-cell lung cancer · New England Journal of Medicine 2024
- NIAGARA: durvalumab before and after cystectomy for muscle-invasive bladder cancer · New England Journal of Medicine 2024
- CheckMate 649: nivolumab plus chemotherapy as first treatment for advanced gastric, gastro-oesophageal junction and oesophageal adenocarcinoma · The Lancet 2021
- IMbrave150: atezolizumab plus bevacizumab replaces sorafenib as first treatment for advanced liver cancer · New England Journal of Medicine 2020
- KEYNOTE-189: pembrolizumab plus chemotherapy as first treatment for non-squamous lung cancer without a driver mutation · New England Journal of Medicine 2018
- PACIFIC: a year of durvalumab after chemoradiotherapy for stage III lung cancer · New England Journal of Medicine 2017
- Iwai and Honjo: tumours use PD-L1 to escape T cells, and blocking it restores attack · PNAS 2002
Latest papers · live from Europe PMC
Query for this target: (TITLE:"PD-L1" OR ABSTRACT:"PD-L1" OR TITLE:"CD274" OR ABSTRACT:"CD274") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about PD-L1, not a curated reading list.
Export
The dossier as machine-readable JSON: identifiers from HGNC, Ensembl, UniProt and ChEMBL, products with status, trials, pathways, hotspots, open questions and assays. The full entity record is in the open API at /api/v1/entities/pdl1.json. Licence CC BY 4.0.