Stains
PDL1

Author: Angela Chan, MSc. (see Authors page)
Editor: Emeka Enwere, Ph.D.

Revised: 8 March 2017, last major update February 2016

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: PDL1 [title]

Cite this page: PDL1. PathologyOutlines.com website. http://pathologyoutlines.com/topic/stainsPDL1.html. Accessed April 30th, 2017.
Definition / general
  • Gene symbol PDCD1LG1 stands for Programmed Cell Death Protein 1 (PDCD1, or PD1) Ligand 1
    • The common term PDL1 stands for Programmed Death Ligand 1
  • It is a member of the B7 family of membrane bound, cell surface ligands
  • Mouse PDL1 is 70% identical to human PDL1
  • The primary receptor for PDL1 is PD1
    • PDL2, a homolog of PDL1, also binds to PD1
  • PDL1 is upregulated in monocytes and other cell types by treatment with interferon gamma (IFN7γ)
  • PDL1 protein is expressed in most human cancers but not in most normal tissues (Nat Med 2002;8:793)
Terminology
  • Alternative names are PDCD1 Ligand 1, PDCD1L1, CD274 or B7H1 (OMIM - PCD1)
Pathophysiology
  • The normal function of the PDL1-PD1 interaction is to protect the host from autoreactive T cells
  • The interaction between PDL1 on presenting cells and PD1 on T cells inhibits T cell activation and cytotoxic T lymphocyte mediated lysis (Nat Med 2002;8:793, Nat Med 1999;5:1365)
  • Binding of PDL1 to PD1 also suppresses T cell migration, suppresses proliferation and secretion of cytotoxic mediators, and restricts tumor cell killing
Clinical features
  • PDL1 expression is detected in most human cancers, including bladder, breast, cervical, esophageal, gastric, kidney, lung, ovary and pancreatic cancers
  • High expression of PDL1 is associated with reduced numbers of tumor infiltrating lymphocytes and poor prognosis (Nat Rev Immunol 2008;8:467), although the reverse has also been noted (Histopathology 2015 Nov 20 [Epub ahead of print])
Uses by pathologists
  • Pembrolizumab and nivolumab are monoclonal antibodies which block the interaction between PDL1 and PD1, and have received FDA approval for specific indications (see below)
  • Pembrolizumab is approved for first line treatment of advanced melanoma
    • Also for second or third line treatment of non small cell lung cancer, but specimens must test positive for PDL1 using a companion FDA approved diagnostic IHC test (DAKO PDL1 IHC 22C3 pharmDx)
    • The recommended cutoff for positive staining using the 22C3 antibody is >50% at any intensity
  • Nivolumab is approved for first line treatment of melanoma, second or third line treatment of non small cell lung cancer, and second or third line treatment of advanced renal cell carcinoma without the requirement for a PDL1 diagnostic test (DAKO PDL1 IHC 28-8 pharmDx), although testing is highly recommended
    • The suggested cutoff for positive staining using the 28-8 antibody is > 1% at any intensity
  • The one assay-one drug approach is not sustainable, because there are multiple IHC antibodies performed on multiple platforms, each with its own scoring criteria
  • Even with the recommendations provided with the IHC assay kits, there is still NO consensus on which antibodies, staining platforms and cut points are suitable across the board (Arch Pathol Lab Med 2016 Jan 12 [Epub ahead of print])
  • Microscopic (histologic) images

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    Placenta



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    Non small cell lung cancer

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    PDL1 prevalence

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    Melanoma samples

    Positive staining - normal
    • Lung macrophages, salivary gland ducts (subsets of cells)
    • Placenta, spleen (diffuse), tonsil (diffuse)
    Positive staining - disease
    • Carcinomas of colorectum, endometrium, liver, lung, ovary, stomach, thyroid
    • Melanoma
    Negative staining
    • Bile duct cells and alveolar cells, hepatocytes, squamous epithelium,