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Programmed death-ligand 1 (PD-L1) expression in various tumor types
© Grosso et al; licensee BioMed Central Ltd. 2013
Published: 7 November 2013
Programmed cell death-1 (PD-1) is a co-inhibitory receptor expressed on lymphoid and non-lymphoid-derived cells that negatively regulates peripheral T-cell responses. PD-L1, the major PD-1 ligand, is expressed on various tumors and is being investigated as a possible predictive marker for anti-PD-1 therapy. Few studies have determined PD-L1 expression across tumor types using a consistent process. We evaluated PD-L1 expression across human tumor samples using a novel, automated, sensitive, and specific PD-L1 IHC assay (developed by Dako) using the 28-8 antibody.
PD-L1 expression in 654 commercially available tumor samples was explored. Percentage of tumor plasma membrane staining was determined at ≥1+ intensity. Macrophage and lymphocyte PD-L1 status was determined by compartment (tumor, non-tumor associated, or both). Immune cell density and PD-L1+ immune cell frequency were assessed on a scale of 0 (none), 1 (mild), 2 (moderate), and 3 (heavy). PD-L1 positivity was evaluated using 5% surface expression values for tumor cell membrane staining.
Of 654 samples examined, spanning 19 tumors from different sites, 89 (14%) were PD-L1+ (≥5% frequency). Highest PD-L1+ frequencies were seen in head and neck (17/54; 31%), cervical (10/34; 29%), cancer of unknown primary origin (CUP; 8/29; 28%), glioblastoma multiforme (GBM; 5/20; 25%), bladder (8/37; 21%), esophageal (16/80; 20%), triple negative (TN) breast (6/33; 18%), and hepatocarcinoma (6/41; 15%). Across a subset of head and neck tumor samples, high PD-L1 expression was seen: lip (2/2; 100%), tongue (2/4; 50%), larynx (11/31; 35%), and oral cavity (2/10; 20%). In breast tumors, TN tumors showed a higher frequency PD-L1+ status (≥5% frequency; 6/33 samples [18%]) compared with estrogen receptor, progesterone receptor, or HER2+ positive tumors (0/45). PD-L1+ was higher in squamous (SQ) compared with other histologies within esophageal (SQ [14/55; 25%] vs other [2/25; 8%]), cervical (SQ [6/15; 40%] vs adenoSQ [2/8; 25%] and adeno [0/5]), and bladder (SQ [3/8; 37%] vs transitional [6/27; 22%]) tumors. PD-L1+ tumors were associated with immune cell density and PD-L1+ immune cells, especially in TN breast and laryngeal tumors.
PD-L1 is expressed in various human tumors and is associated with tumor grade, squamous histology, immune cell density, and co-localization of PD-L1+ immune cells. Highest PD-L1+ frequencies were seen in head and neck, cervical, CUP, GBM, bladder, esophageal, TN breast cancer, and hepatocarcinoma.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.