programmed cell death 1 (CD279) | CD molecules | IUPHAR/BPS Guide to PHARMACOLOGY

programmed cell death 1 (CD279)

Target id: 2760

Nomenclature: programmed cell death 1 (CD279)

Abbreviated Name: PD-1

Family: Other immune checkpoint proteins, CD molecules

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     programmed cell death 1 (CD279) has curated GtoImmuPdb data

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 288 2q37.3 PDCD1 programmed cell death 1
Mouse 1 288 1 D Pdcd1 programmed cell death 1
Rat 1 287 9q36 Pdcd1 programmed cell death 1
Previous and Unofficial Names
Database Links
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the extracellular domain of human PD-1 (Apo-PD-1).
Resolution:  2.1Å
Species:  Human
Natural/Endogenous Ligands
programmed cell death 1 ligand 1 {Sp: Human}

Download all structure-activity data for this target as a CSV file

Key to terms and symbols Click column headers to sort
Antibody Sp. Action Affinity Units Reference
pembrolizumab Hs Binding ~10.0 pKd 3
pKd ~10.0 (Kd ~1x10-10 M) [3]
BGB-A317 Hs Binding 9.8 pKd 4
pKd 9.8 (Kd 1.5x10-10 M) [4]
nivolumab Hs Binding 9.1 pKd 6,9-10
pKd 9.1 (Kd 7.3x10-10 M) [6,9-10]
Antibody Comments
The clinical potential of PD-1 blockade in immuno-oncology is reviewed in [9]. Binding affinity for BGB-A317 should be considered preliminary until reported in a peer reviewed article.
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
programmed cell death 1 ligand 1 {Sp: Human} Hs Binding - -
Immunopharmacology Comments
Immune checkpoint blockade in oncology:
Many types of cancer cells evolve mechanisms to evade control and elimination by the immune system. Such mechanisms can include inhibition of so-called 'immune checkpoints', which would normally be involved in the maintenance of immune homeostasis. An increasingly important area of clinical oncology research is the development of new agents which impede these evasion techniques, thereby switching immune vigilance back on, and effecting immune destruction of cancer cells. Three molecular targets of checkpoint inhibitors which are being extensively pursued are cytotoxic T-lymphocyte antigen 4 (CTLA4), programmed cell death 1 (PD-1), and programmed cell death ligand 1 (PD-L1). Using antibody-based therapies targeting these pathways, clinical responses have been reported in various tumour types, including melanoma, renal cell carcinoma [13] and non-small cell lung cancer [8,11].

Pembrolizumab was the first-in-class, anti-PD-1 antibody to be approved by the US FDA, followed in quick succession by nivolumab. Additional anti-PD-1 mAbs are in various stages of clinical development; e.g. BCD-100 (Biocad; Phase 2/3 melanoma and NSCLC), PDR001 (Novartis; Phase 1-3 in various advanced malignancies, being evaluated in many combination studies with other agents), IBI308 (Innovent Biologics; most advanced study is Phase 3 in advanced or metastatic NSCLC), and SHR-1210 (Jiangsu HengRui Medicine Co; most advanced trials are Phase 3 studies for non-squamous NSCLC and esophageal carcinoma). Cemiplimab (REGN2810; Regeneron) has advanced to Phase 3 evaluation in metastatic NSCLC and recurrent or metastatic, platinum therapy-refractory cervical cancer, with early stage trials in other cancer indications, and a total of 16 active clinical studies listed on Phase 1/2 results in advanced cutaneous squamous cell carcinoma were published in the NEJM in mid 2018 [12].

Synthetic small-molecule PD-1 inhibitors are in development e.g. Curis' CA-170 which is an orally active PD-1/VISTA antagonist in Phase 1 clinical trial (NCT02812875) in patients with advanced solid tumours and lymphomas.

Immune checkpoint blockade in Alzheimer's disease (AD): In mouse models of AD anti-PD-1 antibody treatment was used to induce immune checkpoint blockade. The biological response included an interferon (IFN)-γ-dependent systemic immune response and recruitment of monocyte-derived macrophages to the brain, which was associated with amyloid β plaque clearance and improved cognitive function. These results point to immune checkpoints as valid targets for therapeutic intervention in AD [2].

PD-1 as a new drug target for asthma:
Yu et al. (2016) [14] have identified high PD-1 expression in a population of innate lymphoid cell (ILC) progenitors and activated ILC2 cells. Antibody-induced depletion of PD-1 ILCs reduces cytokine levels in inflammation models, including reducing lung inflammation in a papain-induced asthma model. The authors suggest this may represent an alternative pathway for development of novel immunotherapies for immune disease prevention and control.

The PD-1/PD-L1 axis in the anti-inflammatory effects of mesenchymal stromal cell (MSC) delivery as a novel anti-rejection therapy.
A study that investigated the potential of using MSCs as prophylactic and therapeutic agents against the acute rejection of lung grafts (in rats) identified an MSC-induced upregulation of PD-L1 expression by alveolar cells as a major contributory factor to the anti-inflammatory effects observed, which implicates PD-1/PD-L1 driven inhibition of immune responses in the beneficial effects of MSC therapy [7]. A second significant contributory factor identified was down-regulation of pro-inflammatory IL-17A production by infiltrating effector T cells in the allografts.
Cell Type Associations
Immuno Cell Type:  T cells
Cell Ontology Term:   activated CD4-positive, alpha-beta T cell (CL:0000896)
activated CD8-positive, alpha-beta T cell (CL:0000906)
Comment:  PD-1 expression is induced in murine T cells activated by stimulation through antigen receptors.
References:  1
Immuno Cell Type:  B cells
Cell Ontology Term:   B cell (CL:0000236)
Fraction C precursor B cell (CL:0002049)
Comment:  Expressed in pro-B cells and is thought to play a role in their differentiation. PD-1 expression is induced in murine B cells activated by stimulation through antigen receptors.
References:  1
Immuno Process Associations
Immuno Process:  T cell (activation)
GO Annotations:  Associated to 2 GO processes
GO:0031295 T cell costimulation TAS
GO:0070234 positive regulation of T cell apoptotic process IDA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 2 GO processes
GO:0031295 T cell costimulation TAS
click arrow to show/hide IEA associations
GO:0002644 negative regulation of tolerance induction IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:0031295 T cell costimulation TAS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0031295 T cell costimulation TAS
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0002644 negative regulation of tolerance induction IEA
Clinically-Relevant Mutations and Pathophysiology
Disease:  Alzheimer disease
Synonyms: Alzheimer's disease [Disease Ontology: DOID:10652]
Disease Ontology: DOID:10652
OMIM: 104300
References:  2
Disease:  Multiple sclerosis
Disease Ontology: DOID:2377
OMIM: 126200
Orphanet: ORPHA802
Disease:  Renal cell carcinoma
Disease Ontology: DOID:4450
References:  5
Disease:  Systemic lupus erythematosus, susceptibility to, 2; SLEB2
Synonyms: Systemic lupus erythematosus [Orphanet: ORPHA536] [Disease Ontology: DOID:9074]
Disease Ontology: DOID:9074
OMIM: 605218
Orphanet: ORPHA536
General Comments
The endogenous ligands for human PD-1 are programmed cell death 1 ligand 1 (PD-L1 aka CD274 (CD274, Q9NZQ7) and programmed cell death 1 ligand 2 (PD-L2; PDCD1LG2). These ligands are cell surface peptides, normally involved in immune system regulation.


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1. Agata Y, Kawasaki A, Nishimura H, Ishida Y, Tsubata T, Yagita H, Honjo T. (1996) Expression of the PD-1 antigen on the surface of stimulated mouse T and B lymphocytes. Int. Immunol., 8 (5): 765-72. [PMID:8671665]

2. Baruch K, Deczkowska A, Rosenzweig N, Tsitsou-Kampeli A, Sharif AM, Matcovitch-Natan O, Kertser A, David E, Amit I, Schwartz M. (2016) PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease. Nat. Med., 22 (2): 135-7. [PMID:26779813]

3. Carven GJ, Van Eenennaam H, Dulos GJ. (2010) Antibodies to human programmed death receptor PD-1. Patent number: US20100266617. Assignee: Organon NV. Priority date: 13/06/2008. Publication date: 21/10/2010.

4. Desai J, Markman B, Sandhu SK, Gan HK, Friedlander M, Tran B, Meniawy T, Boolell V, Colyer D, Norris C et al.. A phase I dose-escalation study of BGB-A317, an anti-programmed death-1 (PD-1) mAb in patients with advanced solid tumors. Accessed on 06/06/2017. Modified on 06/06/2017.,

5. FDA. FDA approves nivolumab plus ipilimumab combination for intermediate or poor-risk advanced renal cell carcinoma. Accessed on 18/04/2018. Modified on 18/04/2018.,

6. Hall RD, Gray JE, Chiappori AA. (2013) Beyond the standard of care: a review of novel immunotherapy trials for the treatment of lung cancer. Cancer Control, 20 (1): 22-31. [PMID:23302904]

7. Ishibashi N, Watanabe T, Kanehira M, Watanabe Y, Hoshikawa Y, Notsuda H, Noda M, Sakurada A, Ohkouchi S, Kondo T et al.. (2018) Bone marrow mesenchymal stromal cells protect allograft lung transplants from acute rejection via the PD-L1/IL-17A axis. Surg. Today, 48 (7): 726-734. [PMID:29546496]

8. Johnson DB, Rioth MJ, Horn L. (2014) Immune checkpoint inhibitors in NSCLC. Curr Treat Options Oncol, 15 (4): 658-69. [PMID:25096781]

9. Kline J, Gajewski TF. (2010) Clinical development of mAbs to block the PD1 pathway as an immunotherapy for cancer. Curr Opin Investig Drugs, 11 (12): 1354-9. [PMID:21154117]

10. Korman AJ, Srinivasan M, Wang C, Selby MJ, Chen B, Cardarelli JM. (2006) Human monoclonal antibodies to programmed death 1(pd-1) and methods for treating cancer using anti-pd-1 antibodies alone or in combination with other immunotherapeutics. Patent number: WO2006121168. Assignee: Ono Pharmaceutical Co. Priority date: 09/05/2005. Publication date: 02/03/2015.

11. Malas S, Harrasser M, Lacy KE, Karagiannis SN. (2014) Antibody therapies for melanoma: New and emerging opportunities to activate immunity (Review). Oncol. Rep., 32 (3): 875-86. [PMID:24969320]

12. Migden MR, Rischin D, Schmults CD, Guminski A, Hauschild A, Lewis KD, Chung CH, Hernandez-Aya L, Lim AM, Chang ALS et al.. (2018) PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. N. Engl. J. Med., 379 (4): 341-351. [PMID:29863979]

13. Pal SK, Hu A, Chang M, Figlin RA. (2014) Programmed death-1 inhibition in renal cell carcinoma: clinical insights and future directions. Clin Adv Hematol Oncol, 12 (2): 90-9. [PMID:24892254]

14. Yu Y, Tsang JC, Wang C, Clare S, Wang J, Chen X, Brandt C, Kane L, Campos LS, Lu L et al.. (2016) Single-cell RNA-seq identifies a PD-1hi ILC progenitor and defines its development pathway. Nature, 539 (7627): 102-106. [PMID:27749818]

How to cite this page

CD molecules: programmed cell death 1 (CD279). Last modified on 08/08/2018. Accessed on 23/09/2018. IUPHAR/BPS Guide to PHARMACOLOGY,