PD-L1 expression in gastroenteropancreatic neuroendocrine neoplasms grade 3.

Published on Dec 14, 2020in PLOS ONE3.24
· DOI :10.1371/JOURNAL.PONE.0243900
Abir Salwa Ali5
Estimated H-index: 5
,
Seppo W. Langer26
Estimated H-index: 26
+ 13 AuthorsEva Tiensuu Janson49
Estimated H-index: 49
Sources
Abstract
Gastroenteropancreatic neuroendocrine neoplasms grade 3 (GEP-NENs G3) are rare tumors. These highly aggressive neoplasms are traditionally treated with platinum-based chemotherapy in combination with etoposide. Immune checkpoint proteins such as programmed cell death ligand (PD-L1) may have a role in different cancers allowing them escape the immune system and hence, progress. We aimed to investigate the immunohistochemical expression of PD-L1 in GEP-NEN G3 and evaluate its correlation to clinical parameters. In a cohort of 136 patients, 14 (10%) expressed PD-L1 immunoreactivity; four (3%) patients in the tumor cells and 10 (7%) had immunoreactive immune cells. PD-L1 expression did not correlate to clinical parameters, progression-free survival or overall survival. We conclude that PD-L1 expression is present only in a subset of GEP-NEN G3 patients. Further studies are needed to fully understand the role of PD-L1 in patients with GEP-NEN G3, including the future possibility for treatment with immune checkpoint inhibitors.
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The potential of neuroendocrine neoplasms (NEN) to respond to checkpoint inhibitors is largely unknown and full of great expectations. Immunohistochemical (IHC) studies of programmed cell death ligand 1 (PD-L1) expression in the tumor microenvironment and its implications in predicting the response to checkpoint inhibition is a very active subject. Currently, the combined analysis of PD-L1 expression and tumor-associated immune cell (TAIC) infiltration is considered the best predictive marker of...
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Context.— Regulatory approval of pembrolizumab for treatment of gastric and gastroesophageal junction (G/GEJ) adenocarcinoma required a reproducible scoring method for use of programmed death ligand-1 (PD-L1) protein expression as a companion diagnostic to identify likely responders to therapy. Objective.— To develop an immunohistochemical scoring algorithm that includes PD-L1 expression for tumor and immune cells, that is, the combined positive score. Design.— Four previously treated tumor type...
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Cancer immunotherapy has evolved major breakthroughs in the last years. The cell-surface receptor programmed death-1 (PD-1) and its ligand, programmed death ligand-1 (PD-L1), have been detected in various cancer types. However, the analysis on gastroenteropancreatic neoplasia (GEP-NENs) is limited. Therefore, the aim of this study was to characterize GEP-NENs with regard to PD-1/PD-L1 pathway and tumor-infiltrating lymphocytes (TILs). On protein level, we examined TILs, PD-1 and PD-L1 expression...
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#1Arvind Sahu (University of Melbourne)H-Index: 9
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High-grade gastroenteropancreatic neuroendocrine neoplasms are well-differentiated neuroendocrine tumors or poorly differentiated small/large cell neuroendocrine carcinoma. Distinguishing these entities relies on different genetic backgrounds and resulting different biology. The new classification creates several problems. Almost all clinical treatment data on neuroendocrine neoplasms do not stratify between well and poorly differentiated, providing insufficient help in treatment selection. Trea...
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Neuroendocrine neoplasms (NENs) are rare, heterogeneous and ubiquitous tumors commonly localized in the gastrointestinal tract, lung, and pancreas. The clinical behavior of NEN is highly unpredictable; in fact, low-grade cases can unexpectedly be associated with metastases. Currently, the 2010 WHO NEN classification employs histological differentiation and the proliferation index for grading tumors but fails to provide reliable prognostic and therapeutic indications. Therefore, there is an urgen...
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#1Georg Hutarew (Paracelsus Private Medical University of Salzburg)H-Index: 9
Tumours with high somatic mutation rates escape immune surveillance by upregulating receptors and ligands such as programmed death receptor-1 and its ligand (PD-1/PD-L1). Checkpoint inhibitors (ICI) provide encouraging therapeutic results in non-small cell lung cancers (NSCLC) and may soon be used in 2nd or 1st line therapy. Currently PD-L1 immunohistochemistry (IHC) expression assessed on tumour cells is used as a predictive biomarker, since better patient outcomes are often, but not always ass...
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