Biomarker: PD-L1

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: Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813417, PubMed:28813410). As a ligand for the inhibitory receptor PDCD1/PD-1, modulates the activation threshold of T-cells and limits T-cell effector response (PubMed:11015443, PubMed:28813417, PubMed:28813410). Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10) (PubMed:10581077).4 Publications 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:28813417, PubMed:28813410). The interaction with PDCD1/PD-1 inhibits cytotoxic T lymphocytes (CTLs) effector function (By similarity). 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 (By similarity).

UniProt ID: Q9NZQ7

UniProt Link: https://www.uniprot.org/uniprotkb/Q9NZQ7/entry

Biological function from UniProt: Adaptive immunity, Immunity

Molecular function from UniProt:

Tissue specificity from UniProt: Highly expressed in the heart, skeletal muscle, placenta and lung. Weakly expressed in the thymus, spleen, kidney and liver. Expressed on activated T- and B-cells, dendritic cells, keratinocytes and monocytes

Subcellular UniProt: #Cell membrane #Endosome #Membrane

Alternative name from UniProt:

Recommended name: Programmed cell death 1 ligand 1

Gene name from HGNC: CD274 (B7-H, B7-H1, B7H1, PD-L1, PDCD1LG1, PDL1)

HPA class: Cancer-related genes CD markers Disease related genes FDA approved drug targets

AlphaFold DB: Q9NZQ7

AlphaFold Link: https://alphafold.ebi.ac.uk/entry/Q9NZQ7

Induction: Up-regulated on T- and B-cells, dendritic cells, keratinocytes and monocytes after LPS and IFNG activation. Up-regulated in B-cells activated by surface Ig cross-linking.

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

Tissue specificity RNA from HPA: Tissue enhanced (lung)

Tissue expression from HPA: High expression in placental trophoblasts.

Single cell type specificity Cell type enhanced (Langerhans cells, Syncytiotrophoblasts, monocytes, granulocytes, Extravillous trophoblasts)

Immune cell specificity: Immune cell enhanced (basophil)

Subcellular summary HPA Located in Nucleoplasm, Plasma membrane, Actin filaments

Cancer prognostic summary HPA Prognostic marker in colorectal cancer (favorable) and breast cancer (favorable)

Pathology link: https://www.proteinatlas.org/ENSG00000120217-CD274/pathology

Pathology endo: https://www.proteinatlas.org/ENSG00000120217-CD274/pathology/endometrial+cancer

Disease: No disease ID

Note1: Truncation of the 3'-untranslated (3'-UTR) region of CD274 transcripts leads to elevated expression of CD274 in multiple cancers including T-cell leukemia, diffuse large B-cell lymphoma and stomach adenocarcinoma (PubMed:27281199). Disruption of 3'-UTR region is caused by structural variants that stabilize CD274 transcripts, leading to overexpression (PubMed:27281199). Increased expression in tumors promotes immune evasion and tumor cell growth by allowing malignant cells to escape destruction by the immune system (PubMed:27281199)

OMIM: 605402

OMIM link2: https://www.omim.org/entry/605402

HGNC ID: HGNC:17635

HGNC link: https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:17635