Differences

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--- start [2025/02/21 09:39] – gilbert
+++ start [2025/03/05 15:24] (current) – admin
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 ====== PDL1 in one nutshell ======
+[[Triaging PDL1 3D requests]]
 ===== What is PDL1? =====
 Programmed death-ligand 1 is a protein that in humans is encoded by the CD274 gene. It is a transmembrane protein that **suppresses** the [[Cellular Immunity|cellular immunity]] during particular events such as physiological event like pregnancy, physiopathological event like protecting normal cells in context of infection/inflammation and to prevent autoimmune disease. Cellular immunity is most effective against cells infected with viruses, intracellular bacteria, fungi and protozoans. Malignant cells also take advantage of this protective mechanism to escape immunne surveillance.  The [[keynote001|2015 revolution in immunotherapy]] is based on preventing cancer to escape immune surveillance by inhibiting interaction between **PD1** (expressed by CD8) and **PDL1** (expressed by tumoural cells) using an engineered humanized IgG4 antibody targeting either PD1 or PDL1.
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 **In the upper right picture, two humanized antibodies IgG4 anti-PD1 and anti-PDL1 are respectively represented by a red triangle and an incomplete yellow circle
 **
-===== Triaging PDL1 3D (Diagnosis, Drug, Diagnostic Test) requests =====
-==== Breast ====
-==== Head & Neck ====
-==== Lung ====
-**Assay Purpose:**\\
-**D**iagnostic : Non-small cell lung carcinoma\\
-**D**rug: Pembrolizumab (Merck)\\
-**D**iagnostic test: PDL1 Dako 22C3 pharmDX\\
-**Result: Positive TPS >= 50%**
-**Interpretation**: Tumour Percentage Score (TPS) - Negative (< 1%), Low expression (1-49%), Positive (>= 50%)
-Batch controls: Adequate; On slide controls: Adequate; Immune cell staining: Present;
-Disclaimer: Pembrolizumab is indicated for patients with advanced non-small cell lung carcinoma (stage IIIb and stage IV) whose tumors are PD-L1 positive with a total percentage score (TPS) >= 50% and with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK mutations should have disease progression on authorized therapy for these mutations (EGFR and ALK) prior receiving Pembrolizumab. PD-L1 22C3 pharm Dx was validated with tissue fixed in 10% neutral buffered formalin (NBF) for 12 to 72 hours. The method is not fully validated for shorter or longer fixation in NBF, other fixatives, extended ischemic time, treatment of tissue with microwaves or decalcification. This assay is not interchangeable with other PD-L1 assays and cannot be used for other type of cancers. Batch control includes 2 pelleted, formalin fixed paraffin embedded cell lines: NCI-H226 with moderate PD-L1 protein expression and MCF-7 with negative PD-L1 protein expression. On slide controls include one piece of tonsil (with expected PD-L1 staining positive in immune cells and keratinocytes) and one piece of liver (with expected PD-L1 staining negative in hepatocytes). https://www.nejm.org/doi/full/10.1056/nejmoa1501824
-==== Upper GI ====
 ===== Can I use any PDL1 for any type of tumour? =====