Biomarker: PD-1

Histology type: endometrial carcinoma

Stage: advanced stage

Country: Turkey

Region: Ankara

Study type: retrospective cohort study

Followed up time :

Conclusion: PD-1, PD-L1, and PD-L2 may be a potential target for immunotherapy in elderly and advanced stage EC patients.

Sample type : tissue

Sample method: immunohistochemistry

Expression pattern : positive(total score>2)

Expression elevation: Cytoplasmic and membranous staining of PD-1, PDL1, PD-L2 in tumor and immune cells was accepted as positive.evaluated the combined proportion and intensity. The proportion was scored as: 0, none; <1/100, 1; 1/100 to 1/10, 2; 1/10 to 1/3, 3; 1/3 to 2/3, 4; and >2/3, 5. The intensity was scored as: none, 0; mild, 1; moderate, 2; and strong, 3 . The overall scores (Allred scores) were the sum of the proportion score and intensity score for each patient (range, 0; or from 2 to 8, respectively). The scores were reclassified as “negative” for a total score ≤2 (staining <1% or mild staining),“low” for scores 3 to 4, and “high” for a score ≥5.

Statictics: Mean (SD);Range

Cohort age: 62.9 ± 11.9;35–89

Funtion Uniprot: Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:21276005). Delivers inhibitory signals upon binding to ligands CD274/PDCD1L1 and CD273/PDCD1LG2 (PubMed:21276005). Following T-cell receptor (TCR) engagement, PDCD1 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation (By similarity). Suppresses T-cell activation through the recruitment of PTPN11/SHP-2: following ligand-binding, PDCD1 is phosphorylated within the ITSM motif, leading to the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta (By similarity).By Similarity1 Publication The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and escape destruction by the immune system, thereby facilitating tumor survival (PubMed:28951311). The interaction with CD274/PDCD1L1 inhibits cytotoxic T lymphocytes (CTLs) effector function (PubMed:28951311). The blockage of the PDCD1-mediated pathway results in the reversal of the exhausted T-cell phenotype and the normalization of the anti-tumor response, providing a rationale for cancer immunotherapy (PubMed:22658127, PubMed:25034862, PubMed:25399552).3 Publications1 Publication

UniProt ID: Q15116

UniProt Link: https://www.uniprot.org/uniprotkb/Q15116/entry

Biological function from UniProt: #Adaptive immunity #Apoptosis #Immunity

Molecular function from UniProt:

Tissue specificity from UniProt: Induced at programmed cell death

Subcellular UniProt: #Cell membrane #Membrane

Activity regulation: Inhibited by pembrolizumab (also named MK-3475 or lambrolizumab), a monoclonal antibody that prevents the interaction with CD274/PDCD1L1 (PubMed:27734966, PubMed:27325296). Inhibited by nivolumab (also named ONO-4538, BMS-936558 or Opdivo), a monoclonal antibody that prevents the interaction with CD274/PDCD1L1 (PubMed:28165004). The interaction with nivolumab is not dependent on glycosylation and depends on a loop at the N-terminus (N-terminal loop, corresponding to residues 25-34) (PubMed:28165004). Targeting the interaction between PDCD1 and CD274/PDCD1L1 with pembrolizumab and nivolumab antibodies has demonstrated great promise as a strategy for controlling and eradicating cancer (PubMed:22658127, PubMed:25034862, PubMed:25399552). Pembrolizumab and nivolumab are used for treatment of patients with advanced melanoma (PubMed:25034862, PubMed:25399552). These antibodies are also effective against other cancers, such as non-small cell lung cancer, renal cell carcinoma, bladder cancer and Hodgkin's lymphoma (PubMed:25034862).

Recommended name: Programmed cell death protein 1

Gene name from HGNC: PDCD1 (CD279, hSLE1, PD-1, PD1, SLEB2)

CD antigen name: CD279

HPA class: CD markers Disease related genes FDA approved drug targets Human disease related genes

AlphaFold DB: Q15116

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q15116

HPA link: https://www.proteinatlas.org/ENSG00000188389-PDCD1

Tissue specificity RNA from HPA: Tissue enhanced (heart muscle, lymphoid tissue)

Tissue expression from HPA: Cytoplasmic expression in a subset of cells in lymphoid germinal centers.

Single cell type specificity Group enriched (T-cells, Plasma cells)

Immune cell specificity: Group enriched (memory CD8 T-cell, memory CD4 T-cell, MAIT T-cell, gdT-cell, T-reg)

Cancer prognostic summary HPA Prognostic marker in renal cancer (unfavorable) and endometrial cancer (favorable)

Pathology link: https://www.proteinatlas.org/ENSG00000188389-PDCD1/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000188389-PDCD1/pathology/endometrial+cancer

Phenotype ID: 605218

Disease: Systemic lupus erythematosus 2 (SLEB2)

Note1: Disease susceptibility is associated with variants affecting the gene represented in this entry

OMIM: 600244

OMIM link1: https://www.omim.org/entry/605218

OMIM link2: https://www.omim.org/entry/600244

HGNC ID: HGNC:8760

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:8760