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PD1


Official Full Name
programmed cell death 1
Organism
Homo sapiens
Gene ID
5133
Background
Programmed cell death protein 1 (PDCD1) is an immune-inhibitory receptor expressed in activated T cells; it is involved in the regulation of T-cell functions, including those of effector CD8+ T cells. In addition, this protein can also promote the differentiation of CD4+ T cells into T regulatory cells. PDCD1 is expressed in many types of tumors including melanomas, and has demonstrated to play a role in anti-tumor immunity. Moreover, this protein has been shown to be involved in safeguarding against autoimmunity, however, it can also contribute to the inhibition of effective anti-tumor and anti-microbial immunity. [provided by RefSeq, Aug 2020]
Synonyms
PD1; PD-1; CD279; SLEB2; hPD-1; hPD-l; hSLE1; AIMTBS
Bio Chemical Class
Immunoglobulin
Protein Sequence
MQIPQAPWPVVWAVLQLGWRPGWFLDSPDRPWNPPTFSPALLVVTEGDNATFTCSFSNTSESFVLNWYRMSPSNQTDKLAAFPEDRSQPGQDCRFRVTQLPNGRDFHMSVVRARRNDSGTYLCGAISLAPKAQIKESLRAELRVTERRAEVPTAHPSPSPRPAGQFQTLVVGVVGGLLGSLVLLVWVLAVICSRAARGTIGARRTGQPLKEDPSAVPVFSVDYGELDFQWREKTPEPPVPCVPEQTEYATIVFPSGMGTSSPARRGSADGPRSAQPLRPEDGHCSWPL
Open
Disease
Bladder cancer, Brain cancer, Breast cancer, Cervical cancer, Colorectal cancer, Diffuse large B-cell lymphoma, Endometrial cancer, Epidermal dysplasias, Esophageal cancer, Follicular lymphoma, Hodgkin lymphoma, Human immunodeficiency virus disease, Inflammatory liver disease, Liver cancer, Lung cancer, Lymphoma, Malignant haematopoietic neoplasm, Melanoma, Metastatic tumour, Multiple myeloma, Myeloproliferative neoplasm, Nasopharyngeal cancer, Neuroendocrine carcinoma, Non-small-cell lung cancer, Oral cavity/oesophagus/stomach in situ carcinoma, Ovarian cancer, Pancreatic cancer, Penile cancer, Pleural mesothelioma, Postoperative inflammation, Prostate cancer, Psoriasis, Renal cell carcinoma, Rheumatoid arthritis, Solid tumour/cancer, Squamous cell carcinoma, Stomach cancer, Ulcerative colitis, Ureteral cancer, Uterine ligament/parametrium/uterine adnexa neoplasm
Approved Drug
9 +
Clinical Trial Drug
50 +
Discontinued Drug
0

Cat.No. Product Name Price
CSC-DC011479 Panoply™ Human PDCD1 Knockdown Stable Cell Line Inquiry
CSC-RO0871 Mouse Pdcd1 Stable Cell Line - HEK293T Inquiry
CSC-RO0847 Human PDCD1 Stable Cell Line - M-07e Inquiry
CSC-RO0670 Human CD274(-)/PDCD1 Stable Cell Line Inquiry
CSC-RT2658 Human PDCD1 Knockout Cell Line-NCI-H1299 Inquiry
CSC-RT2657 Human PDCD1 Knockout Cell Line-786-O Inquiry
CLOE-2897 Mouse Pdcd1 (His) HEK293 Cell Lysate Inquiry
CLOE-2893 Mouse Pdcd1 (Fc) HEK293 Cell Lysate Inquiry
CLOE-1888 Rat Pdcd1 (His) HEK293 Cell Lysate Inquiry
CLOE-1887 Rat Pdcd1 (Fc) HEK293 Cell Lysate Inquiry
CLOE-1464 Human PDCD1 HEK293 Cell Lysate Inquiry
CSC-RO0209 Human PDCD1 Stable Cell Line - Daudi Inquiry
CSC-RO0111 Human PDCD1 Stable Cell Line-HEK293T Inquiry
CSC-RO0069 Human PDCD1 Stable Cell Line-CHO-K1 Inquiry
CSC-RO0049 Mouse Pdcd1 Stable Cell Line-CHO-K1 Inquiry
CSC-RO0010 Human SPATA2 Stable Cell Line-CHO-K1 Inquiry
CSC-RT2474 Human PDCD1 Knockout Cell Line-Hela Inquiry
CSC-SC014980 Panoply™ Human SPATA2 Over-expressing Stable Cell Line Inquiry
CSC-SC013507 Panoply™ Human RPL17-C18ORF32 Over-expressing Stable Cell Line Inquiry
CSC-SC013506 Panoply™ Human RPL17 Over-expressing Stable Cell Line Inquiry
CSC-SC011479 Panoply™ Human PDCD1 Over-expressing Stable Cell Line Inquiry
CSC-DC014980 Panoply™ Human SPATA2 Knockdown Stable Cell Line Inquiry
CSC-DC013507 Panoply™ Human RPL17-C18ORF32 Knockdown Stable Cell Line Inquiry
CSC-DC013506 Panoply™ Human RPL17 Knockdown Stable Cell Line Inquiry
CSC-RO02534 Human SNCA Stable Cell Line - SH-SY5Y Inquiry
CSC-RT2824 Human SNCA Knockout Cell Line-HEK293T Inquiry
Cat.No. Product Name Price
SHH372140 shRNA set against Human PDCD1 (NM_005018.2) Inquiry
SHH372144 shRNA set against Mouse PDCD1 (NM_008798.2) Inquiry
SHH372148 shRNA set against Rat PDCD1 (NM_001106927.1) Inquiry
SHW010933 shRNA set against Danio rerio SPATA2 (NM_001080191) Inquiry
SHW000726 shRNA set against Chicken SPATA2 (NM_001007873) Inquiry
SHL021312 shRNA set against Rat Snca(NM_019169.2) Inquiry
SHW005182 shRNA set against Chicken SNCA (NM_204673) Inquiry
SHW004389 shRNA set against Chicken RPL17 (NM_001282277) Inquiry
SHR190806 shRNA set against Mouse Rpl17(NM_001002239.3) Inquiry
SHR190770 shRNA set against Rat Rpl17(NM_201415.1) Inquiry
SHR066714 shRNA set against Rat Olr707_predicted(NM_001001065.1) Inquiry
SHR066678 shRNA set against Rat Olr703_predicted(NM_001000359.1) Inquiry
SHL026742 shRNA set against Mouse Spata2(NM_170756.2) Inquiry
SHL026706 shRNA set against Rat Spata2(NM_053675.2) Inquiry
SHL021384 shRNA set against Mouse Snca(NM_009221.2) Inquiry
SHW013919 shRNA set against Danio rerio RPL17 (NM_001243037) Inquiry
SHL021284 shRNA set against Mouse Snca(NM_001042451.1) Inquiry
SHL021262 shRNA set against Mouse Snca(NM_009221.2) Inquiry
SHH416092 shRNA set against Rat SPATA2 (NM_053675.2) Inquiry
SHH416088 shRNA set against Mouse SPATA2 (NM_170756.2) Inquiry
SHH414000 shRNA set against Rat SNCA (NM_019169.2) Inquiry
SHH413996 shRNA set against Mouse SNCA (NM_009221.2) Inquiry
SHH398224 shRNA set against Rat RPL17 (NM_201415.1) Inquiry
SHH398220 shRNA set against Mouse RPL17 (NM_001002239.3) Inquiry
SHL021398 shRNA set against Mouse Snca(NM_001042451.1) Inquiry
SHW017916 shRNA set against Danio rerio RPL17 (NM_212760) Inquiry
Cat.No. Product Name Price
CDCB157215 Mouse PDCD1 ORF clone (NM_008798.1) Inquiry
CDFH018431 Human SPATA2 cDNA Clone(NM_001135773.1) Inquiry
CDFR006281 Rat Pdcd1 cDNA Clone(NM_001106927.1) Inquiry
CDFR011467 Rat Snca cDNA Clone(NM_019169.2) Inquiry
CDFR013386 Rat Spata2 cDNA Clone(NM_053675.2) Inquiry
CDFR015285 Rat Rpl17 cDNA Clone(NM_201415.1) Inquiry
MiUTR1H-07692 PDCD1 miRNA 3'UTR clone Inquiry
MiUTR1H-09818 SPATA2 miRNA 3'UTR clone Inquiry
MiUTR1M-10238 RPL17 miRNA 3'UTR clone Inquiry
MiUTR1M-11026 SNCA miRNA 3'UTR clone Inquiry
MiUTR1M-11027 SNCA miRNA 3'UTR clone Inquiry
MiUTR1M-11132 SPATA2 miRNA 3'UTR clone Inquiry
MiUTR1R-07033 RPL17 miRNA 3'UTR clone Inquiry
MiUTR1R-07587 SNCA miRNA 3'UTR clone Inquiry
MiUTR1R-07637 SPATA2 miRNA 3'UTR clone Inquiry
MiUTR4H-TG07648 RPL17 miRNA 3'UTR clone Inquiry
MiUTR4H-TG08442 SPATA2 miRNA 3'UTR clone Inquiry
CDCR373704 Rat Pdcd1 ORF Clone(NM_001106927.1) Inquiry
CDCR380473 Rat Spata2 ORF Clone(NM_053675.2) Inquiry
CDCH075162 human RPL17 ORF clone (NM_001199345.1) Inquiry
CDCB160259 Human SNCA ORF clone (NM_000345.3) Inquiry
CDCB162201 Chicken SPATA2 ORF Clone (NM_001007873) Inquiry
CDCB166657 Chicken SNCA ORF Clone (NM_204673) Inquiry
CDCB194044 Rabbit RPL17 ORF clone (XM_002713529.2) Inquiry
CDCR246148 Mouse Pdcd1 ORF Clone(NM_008798.2) Inquiry
CDCH083946 Mouse Snca ORF clone (NM_009221.2) Inquiry
SKO0797 SNCA Validated sgRNA vector Inquiry
CDCR233609 Mouse Snca ORF Clone(NM_001042451.1) Inquiry
CDCS408129 Human SPATA2 ORF Clone (BC009481) Inquiry
CDCR378510 Rat Snca ORF Clone(NM_019169.2) Inquiry
CDCB165864 Chicken RPL17 ORF Clone (NM_001282277) Inquiry
CDCR037378 Human RPL17-C18ORF32 ORF clone (NM_001199356.1) Inquiry
CDCB172408 Danio rerio SPATA2 ORF Clone (NM_001080191) Inquiry
CDCB175394 Danio rerio RPL17 ORF Clone (NM_001243037) Inquiry
CDCB179391 Danio rerio RPL17 ORF Clone (NM_212760) Inquiry
CDCB182366 Rabbit SNCA ORF clone (XM_008267597.1) Inquiry
CDCB187301 Rabbit SPATA2 ORF clone (XM_008251759.1) Inquiry
CDCB191459 Rabbit PDCD1 ORF clone (XM_002723727.2) Inquiry
CDCR382361 Rat Rpl17 ORF Clone(NM_201415.1) Inquiry
CDCS405594 Human SNCA ORF Clone (BC013293) Inquiry
CDCS406051 Human RPL17 ORF Clone (BC000502) Inquiry
CDCH084982 Mouse Spata2 ORF clone (NM_170756.2) Inquiry
CDCL185646 Human PD1 ORF clone(NM_005018.2) Inquiry
CDCS406052 Human RPL17 ORF Clone (BC066324) Inquiry
CDCR350502 Human SPATA2 ORF Clone(NM_001135773.1) Inquiry

Detailed Information

PD1 is a type I transmembrane glycoprotein with a molecular weight of 50-55 kD. It belongs to the immunoglobulin superfamily B7-CD28 and is an important immunosuppressive receptor. It is mainly expressed in activated T cells, B cells,and natural killing cells, monocytes, and mesenchymal stem cells. PD1 is an important factor in maintaining self-tolerance. Under physiological conditions, PD1 recognizes antigen through T cell receptor TCR (T cell receptor), regulates the function of T cells in peripheral tissues, and regulates the immune response of the body to foreign or autoantigens, preventing the occurrence of immune-related diseases.

PD-L1 and PD-L2 are ligands for PD1 and are important negative regulators in the immune response. The two functions are similar. The main function is to inhibit cell cycle arrest by inhibiting T cell receptor-mediated B cell proliferation and interleukin 2, 10, interferon gamma and other cytokines by binding to PD1, thereby inhibiting T cell activation.

PD1.pngFigure 1. Effect of PD-1 on major signaling pathways and subsequent metabolic reprograming in T cells. (Kankana, B., et al. 2016)

PD1/PD-L1 and Tumor Immunity

Under normal circumstances, the body's complete immune mechanism can effectively monitor and eliminate cancer cells. Therefore, most individuals do not have tumor growth, and patients with tumors are not prone to distant metastasis. Under physiological conditions, PD-L1 on the surface of normal tissue cells can bind to PD1 on the surface of lymphocytes, inhibit the function of lymphocytes, and induce the apoptosis of activated lymphocytes, thereby preventing autoimmune damage and protecting normal tissues and organs.

Under pathological conditions, the tumor microenvironment induces infiltration of T cells to express PD-1 molecules, and tumor cells highly express PD1 ligands PD-L1 and PD-L2, resulting in continuous activation of PD1 pathway in tumor microenvironment. When PD-L1 linked to PD1, T cell function is inhibited, weakening or blocking its ability to send signals to the immune system that attack the tumor. The PD1/PD-L1 inhibitor can block the binding of PD1 to PD-L1, block the negative regulatory signal, and restore the T cell to activate the immune response. It is shown that blocking PD1 binding to ligands can strengthen and maintain endogenous anti-tumor effects, allowing tumors to be more permanently controlled. Clinical studies have also found that inhibitors of PD1 and PD-L1 have been shown to be effective and well-preserved in a variety of tumors, particularly advanced melanoma and non-small cell lung cancer.

Expression of PD1 in Tumors

PD-L1 is significantly elevated in tumor tissues compared with normal tissues and is expressed on the surface of most tumor cells, including non-small cell lung cancer, melanoma, gastric cancer, colon cancer, breast cancer, pancreatic cancer, and kidney cancer. Koh et al found that PD1 is associated with poor prognosis in patients with classical Hodgkin's lymphoma, and that lowering the expression level of PD1 can improve overall survival. RS (Reed-Sternberg) cells are characteristic cells of Hodgkin's lymphoma with a high surface expressing PD-L1. When PD-L1 overexpressed on RS cells binds to the corresponding receptor PD1, it can inhibit the proliferation and activation of T cells, promote the growth of RS cells, and produce metastases.

Circulating tumor cells (CTC) are an important predictor of immunological checkpoint blockade therapy. The study found that CTC mediates the distant metastasis of tumor cells by regulating the expression level of PD-L1, and the transfer and tumor formation ability of CTC circulating colonies is 23 to 50 times that of single CTC. The study found that 11 (68.6%) of 16 patients with metastatic breast cancer with CTC had high expression of PD-L1. It is suggested that CTC can be regulated by targeted intervention of PD-L1 to reduce metastasis and recurrence of breast cancer.

Both PD1 and Treg cells are involved in distant metastasis and recurrence of tumors, and high levels of PD1 can enhance the inhibitory function of Treg cells. Some lymphocyte chemokines such as CCL2, CXCR2, and CXCL5 can increase the expression level of PD-L1, induce the occurrence of EMT, and promote the invasion and metastasis of cancer. Blocking the expression of CXCR2 can increase the sensitivity of PD1 antibody to immunotherapy, increase the infiltration of CD3+ T cells in tumor tissues and the activity of CD4+ and CD8+ T cells, and inhibit tumor invasion and metastasis.

PD1/PD-L1 Antibody in Tumor Immunotherapy

Nivolumab, a monoclonal antibody against PD1, restores the activity of T cells against tumor immune responses. In 2017, Bristol-Myers Squibb (BMS) announced the latest data on Nivolumab's single-agent use in 214 patients with advanced liver cancer. 43 patients had tumor shrinkage of at least 30% and objective efficiency increased to 20%; 64 patients had stable tumors. The disease control rate is as high as 64%; the September survival rate is 74%; the 3~4 grade adverse reaction rate is 20%. The latest phase III clinical trial results show for the first time that Nivolumab can significantly prolong the survival of patients with advanced gastric cancer.

Pembrolizumab is the first humanized PD1 monoclonal antibody marketed in the United States as a second-line drug for the treatment of melanoma. Goldberg et al. enrolled 52 patients with melanoma brain metastasis with positive PD-L1 expression and patients with non-small cell lung cancer with brain metastasis. The results showed that the objective response rate of patients with melanoma brain metastases was 22%, non-small cell lung cancer. The objective response rate of patients with brain metastases was 33%.

Atezolizumab is the first FDA-approved anti-PD-L1 immunotherapeutic for immunotherapy of bladder cancer and metastatic non-small cell lung cancer. In a Phase II clinical trial of cisplatin-treated late or metastatic urothelial cancer, the results showed that Atezolizumab treatment reduced tumor volume in 15% of patients. In patients with high PD-L1 expression, Atezolizumab treatment reduced tumor volume in 26% of patients. This indicates that the higher the level of PD-L1 expression in the patient's tumor, the greater the degree of remission achieved.

References:

  1. (2017). Atezolizumab (tecentriq) for bladder cancer and nsclc. Medical Letter on Drugs & Therapeutics, 59(1515), e40.
  2. Trojan, J. , & Sarrazin, C. . (2016). Complete response of hepatocellular carcinoma in a patient with end-stage liver disease treated with nivolumab: whishful thinking or possible|[quest]|. American Journal of Gastroenterology, 111(8), 1208.
  3. Goldberg, S. B. , Gettinger, S. N. , Mahajan, A. , Chiang, A. C. , Herbst, R. S. , & Sznol, M. , et al. (2016). A phase ii trial of pembrolizumab for patients with melanoma or non-small cell lung cancer and untreated brain metastases. Lancet Oncology,17(7), 976.
  4. Wang, X. , Sun, Q. , Liu, Q. , Wang, C. , Yao, R. , & Wang, Y. . (2016). Ctc immune escape mediated by pd-l1. Medical Hypotheses, 93, 138-139.
  5. Koh, Y. W. , Jeon, Y. K. , Yoon, D. H. , Suh, C. , & Huh, J. . (2016). Programmed death 1 expression in the peritumoral microenvironment is associated with a poorer prognosis in classical hodgkin lymphoma. Tumor Biology, 37(6), 7507-7514.
  6. Kankana, B. , Theodora, A. , & Boussiotis, V. A. . (2016). The pd1:pd-l1/2 pathway from discovery to clinical implementation. Frontiers in Immunology, 7.
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