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PD-L1 is the tumour's side of the PD-1 brake, and also the biomarker that decides who gets immunotherapy.
PD-L1 (CD274) is the tumour-side ligand of the PD-1 brake, expressed on tumour and immune cells and induced by interferon-gamma, so its presence often marks an immune response already under way. Atezolizumab, durvalumab and avelumab block it directly. PD-L1 immunohistochemistry (22C3 CPS, SP142, 28-8) is the companion diagnostic for many indications, including CPS 10 or above for pembrolizumab in triple-negative breast cancer, with prevalence from 25 to 30 percent of NSCLC at TPS 50 percent or more to 80 to 85 percent of head and neck cancers at CPS 1 or more. Differing assays and cut-offs across drugs remain a practical source of confusion. It is now also an ADC and bispecific target (PD-L1×B7-H3 ADC BH4601, PD-L1×VEGF bispecifics). PD-L1 is both the target of immunotherapy and the test that decides who receives it.
In plain words · PD-L1 is the tumour's side of the PD-1 brake, and also the biomarker that decides who gets immunotherapy.
Backbone ribbon from PDB 5X8L. RCSB PDB 5X8L. The ribbon widens where the chain is folded into a regular pattern and narrows where it is a loose loop.
PD-L1 is the tumour's side of the PD-1 brake, and also the biomarker that decides who gets immunotherapy.
Expressed on tumour and immune cells; induced by interferon-gamma.
25 products aim at PD-L1: antibodies, antibody-drug conjugates, bispecific antibodies, vaccines, small molecules and other agents. Checkpoint drugs are antibodies that cover one side of an immune ‘stand down’ handshake so T cells stay active.
The first head-to-head test of the PD-1 x VEGF bispecific against pembrolizumab in a Western population. Timing is our estimate from the registry record; the sponsor has not given a date. Source
Immune or microenvironment target: the record's class is immune checkpoint. HPA CD274: RNA tissue enhanced (lung 16 nTPM); blood lineage lineage enriched (granulocytes 7 nTPM); high antibody staining in 2 normal tissues; highest cancer staining cervical cancer (1 of 11 high). Distribution: 9 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Breast cancer (all types), Lung cancer (all types), Head and neck squamous cell carcinoma, Bladder & urothelial cancer, Biliary tract cancer (all types), Gastric & gastro-oesophageal junction cancer, Oesophageal cancer and more); approvals of single-target medicines aimed at it also list Hepatocellular carcinoma, Sarcomas (soft tissue, bone, GIST), Renal cell carcinoma, Skin cancer (all types) and more, not counted; Open Targets associates it with 8 specific cancer types at or above 0.5 (non-small cell lung carcinoma, Merkel cell skin cancer, small cell lung carcinoma, hepatocellular carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma and more). Tissue-agnostic: Envafolimab China 2021: "Previously treated MSI-H or dMMR advanced solid tumours". (Rule 1 of scripts/fetch-target-specificity.ts.)
Sources: Human Protein Atlas CD274 tissue; UniProt Q9NZQ7; Open Targets ENSG00000120217 associations
First described 1999. Earliest sequence paper UniProt cites for the protein: Dong et al, Nat. Med, 1999, "B7-H1, a third member of the B7 family, co-stimulates T-cell proliferation and interleukin-10 secretion". Source.
What a pathology or genomic report can say about this target, each with the thresholds approvals use.
Expressed on tumour and immune cells; induced by interferon-gamma.
RNA: tissue enhanced (lung 16 nTPM), detected in many normal tissues. Blood: lineage enriched (granulocytes 7 nTPM).
Medium: Appendix, Lung, Tonsil.
Medium only: breast cancer, carcinoid, glioma, renal cancer.
HPA CD274 tissue · HPA CD274 pathology · HPA protein class: CD markers, FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Head and neck squamous cell carcinoma | 80-85% | CPS >=1 | KEYNOTE-048 | Wikipedia |
| Triple-negative breast cancer | 41-51% | IC 1% or more (SP142) | 46.4% of 614 centrally scored IMpassion130 samples (Rugo 2021); 50.9% of 232 population-based early TNBCs (Sigurjonsdottir 2023); the IMpassion130 PD-L1-positive subgroup was defined by this score (Schmid 2018). | doi.org |
| Triple-negative breast cancer | 35-40% | CPS >=10 (22C3), metastatic | KEYNOTE-355 screening | Wikipedia |
| Triple-negative breast cancer | 27-38% | CPS 10 or more (22C3) | The CPS-10 subgroup of KEYNOTE-355 carried the overall survival benefit, 23.0 versus 16.1 months (Cortes 2022); 27.2% of 232 early TNBCs, with CPS 1 or more in 53.9% (Sigurjonsdottir 2023); harmonised CPS 10 concordance with SP142 IC 1% was about 75% in IMpassion130 (Rugo 2021). cBioPortal: CD274 amplification in 8 of 119, 6.7%, in brca_tcga_pan_can_atlas_2018 and 20 of 320, 6.2%, in brca_metabric. | doi.org |
| Non-small-cell lung cancer | 25-30% | TPS >=50% | ~60-65% TPS >=1% | Wikipedia |
| Bladder & urothelial cancer | 25-30% | CPS >=10 | Wikipedia | |
| Gallbladder cancer | 15-23% | Protein expression (IHC) | Tumour cells positive at 1% or more in 23.0% of 174 Indian cases (SP263; 14.9% at 10% and 7.5% at 50%), with PD-L1 on immune cells in 24.1% (Neyaz 2018); tumour proportion score 1% or more in 14.7% of 131 Western cases, 4.7% above 10% and 3.1% above 25% (Albrecht 2021); 98% of 47 United States adenocarcinomas stained with a different antibody and scoring (Patil 2021). | doi.org |
| 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.
Acasunlimab is an experimental bispecific antibody from Genmab in phase 3 trials for non-small-cell lung cancer, aimed at PD-L1.
Adebrelimab is Hengrui's PD-L1 antibody, approved in China for first-line extensive-stage small cell lung cancer on the CAPSTONE-1 trial.
A PD-L1 blocker used in lung, liver, and bladder cancer. In 2026 it became the first drug approved based on a blood test showing leftover cancer after bladder surgery.
Avelumab is a PD-L1 blocker given as maintenance after chemotherapy for advanced bladder cancer, which lengthened survival by about seven months.
Benmelstobart is Chia Tai Tianqing's PD-L1 antibody, approved in China in 2024 for extensive-stage small-cell lung cancer in combination with anlotinib and chemotherapy.
Cosibelimab is a PD-L1 antibody approved in December 2024 for advanced cutaneous squamous cell carcinoma, offering a third immunotherapy choice.
A PD-L1 blocker that became standard after chemoradiation for stage III lung cancer, and now in bladder, biliary, and gastric cancers.
Envafolimab is the first PD-L1 antibody given as a quick injection under the skin rather than an infusion, approved in China for advanced tumours with mismatch-repair deficiency.
HB0036 is an experimental investigational agent whose form is not stated in the registry from Shanghai Huaota Biopharmaceutical in phase 2 trials for non-small-cell lung cancer, aimed at PD-L1 and TIGIT.
HLX43 is an experimental antibody-drug conjugate from Shanghai Henlius Biotech in phase 3 trials for non-small-cell lung cancer, cervical cancer and ovarian cancer, aimed at PD-L1 and EGFR.
IO102-IO103 is an experimental peptide (immunotherapeutic vaccine) from IO Biotech in phase 3 trials for melanoma and head and neck squamous cell carcinoma, aimed at PD-L1.
QL1706 is Qilu Pharmaceutical's PD-1 plus CTLA-4 antibody mixture, approved in China in 2024 for recurrent or metastatic cervical cancer after platinum chemotherapy.
The 22C3 pharmDx assay is the PD-L1 stain tied to pembrolizumab since 2015 and the source of the combined positive score (CPS). The cut-off differs by cancer: 1% of tumour cells in lung cancer, CPS 1 in gastric, cervical and head and neck cancer, CPS 10 in oesophageal and triple-negative breast cancer, so one stain is read differently per disease.
PF-08046054 is an experimental antibody-drug conjugate from Pfizer in phase 3 trials for non-small-cell lung cancer, aimed at PD-L1.
PM8002 is an experimental bispecific antibody from Biotheus in phase 3 trials for small-cell lung cancer, triple-negative breast cancer and neuroendocrine tumours, aimed at PD-L1 and VEGF / VEGFR.
Retlirafusp alfa is Hengrui's PD-L1 and TGF-beta bifunctional antibody, in phase 3 trials with chemotherapy in gastric cancer after the Western class leader bintrafusp alfa failed.
Sasanlimab is an experimental monoclonal antibody from Pfizer in phase 3 trials for bladder & urothelial cancer, aimed at PD-1 and PD-L1.
Socazolimab is Lee's Pharmaceutical's PD-L1 antibody, in phase 3 trials in China for extensive-stage small cell lung cancer and recurrent cervical cancer.
SSGJ-706 is an experimental bispecific antibody from Shenyang Sunshine Pharmaceutical in phase 2 trials for non-small-cell lung cancer, aimed at PD-1 and PD-L1.
Sugemalimab is CStone's PD-L1 antibody, approved in China for first-line lung cancer with chemotherapy and after chemoradiotherapy in stage III disease, and the first China-developed PD-L1 antibody to win European approval.
T3011 is an experimental small-molecule drug from ImmVira Pharma in phase 2 trials for melanoma, head and neck squamous cell carcinoma and sarcomas, aimed at PD-1 and PD-L1.
An immune-brake blocker that looked excellent in a phase 2 lung cancer trial and then failed every phase 3.
TQB2450 is an experimental monoclonal antibody from Chia Tai Tianqing Pharmaceutical in phase 3 trials for renal cell carcinoma and non-small-cell lung cancer, aimed at PD-L1 and PD-1.
The PD-L1 stain that decides who can have atezolizumab, scored on immune cells rather than tumour cells in breast cancer.
The VENTANA SP263 assay is an immunohistochemistry stain that measures PD-L1 on tumour cells. Approved in 2017 alongside durvalumab in bladder cancer, it became the companion test in 2021 for adjuvant atezolizumab in resected lung cancer with PD-L1 on at least 1% of tumour cells, and it agrees closely with 22C3, so laboratories often validate it as a single platform.
The 48 most recent of 55 papers; see them all →
After bladder removal, a blood test can now tell who needs immunotherapy and who can safely be spared it. This is the model for MRD-guided adjuvant therapy across cancers: treat the blood-positive, watch the blood-negative.
Patients with limited-stage small-cell lung cancer who complete chemoradiotherapy without progression should now be offered up to two years of durvalumab consolidation, which extends life by almost two years on average. This is the first survival improvement for limited-stage disease since twice-daily radiotherapy and prophylactic cranial irradiation, and small-cell lung cancer is no longer a disease where immunotherapy gives only marginal gains.
Patients fit enough for cisplatin whose bladder cancer has invaded the muscle wall should now be offered durvalumab with their pre-operative chemotherapy and for about a year after surgery, which improves the chance of cure without compromising the operation. The trial cannot say whether the adjuvant phase is necessary, or how to treat cisplatin-ineligible patients, for whom other trials are ongoing.
It is the positive half of the tumour mutational burden story and it applies only to single-agent immunotherapy, which is the setting fewest patients are treated in.
This is the result that ended tumour mutational burden as a practical selector in lung cancer: in the regimen most patients receive, it selects nobody, and neither do the co-mutations most often quoted as reasons to withhold immunotherapy.
This is the population-based prevalence for the two label thresholds in early TNBC, and it shows the KEYNOTE-355 CPS 10 gate would admit only about a quarter of unselected patients.
This cohort, with the locally advanced cohort in the label, is the evidence behind cosibelimab's December 2024 US approval. The response rate is of the same order as cemiplimab and pembrolizumab in this cancer, which gives patients a third checkpoint antibody option, though none of the three has been compared head to head.
Perioperative immunotherapy is now standard for resectable lung cancer without a targetable driver. The updated overall survival hazard ratio of 0.89, with a confidence interval crossing one, is the honest state of the evidence on whether it cures more people.
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.
Shares An Early Phase Trial of RPTR-1-201 in Advanced Solid Tumors, Imaging Advanced NSCLC Patients Undergoing PD-1/PD-L1 Directed Therapy Using [18F]-FARAG, Personalised Neoantigen-targeting Cancer Vaccine NECVAX-NEO1 in Anti-PD-1/PD-L1 Therapy in Patients With Solid Tumors, Insight Molecular Diagnostics (formerly Oncocyte) and the tag checkpoint.
Shares Durvalumab with or without tremelimumab for patients with metastatic pancreatic ductal adenocarcinoma: a phase 2 randomized clinical trial, HIMALAYA, Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden, Ribas and Wolchok 2018: cancer immunotherapy using checkpoint blockade and the tag checkpoint.
Shares Pardoll 2012: the blockade of immune checkpoints in cancer immunotherapy, Hallmark: avoiding immune destruction, T cell, T-cell exhaustion and the tag checkpoint.
Shares Recurrent and metastatic nasopharyngeal carcinoma, Oncogenic viruses, Nasopharyngeal carcinoma, Hodgkin lymphoma and the tag biomarker.
Shares Blood-based tumor mutational burden as a predictor of clinical benefit in non-small-cell lung cancer patients treated with atezolizumab, CheckMate 026: first-line nivolumab in stage IV or recurrent non-small-cell lung cancer, Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden, Tumor mutational burden and PTEN alterations as molecular correlates of response to PD-1/L1 blockade in metastatic triple-negative breast cancer and the tag biomarker.
Shares HB0036, Caution: TIGIT + PD-(L)1 blockade, Tiragolumab, T-cell exhaustion and the tag checkpoint.
Shares Associations of tissue tumour mutational burden and mutational status with clinical outcomes with pembrolizumab plus chemotherapy versus chemotherapy for metastatic non-small-cell lung cancer, Associations of tissue tumour mutational burden and mutational status with clinical outcomes in KEYNOTE-042, STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS -Mutant Lung Adenocarcinoma, Diminished efficacy of programmed death-(ligand)1 inhibition in STK11- and KEAP1-mutant lung adenocarcinoma is affected by KRAS mutation status and the tag biomarker.
Shares The Hodgkin microenvironment: when the cancer cell is the minority, JAK-STAT signalling, Antigen presentation & immune editing, Primary mediastinal (thymic) large B-cell lymphoma and the tag biomarker.