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Spatial distribution of immune checkpoint proteins in histological subtypes of lung adenocarcinoma

The most prevalent histological type of non-small cell lung cancer (NSCLC) is adenocarcinoma. The WHO classifies this tumor into subtypes according to the predominant growth pattern such as lepidic, acinar, papillary, solid or micropapillary, each harboring specific molecular features. NSCLC adenoca...

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Autores principales: Müller, Sarah, Mayer, Stefanie, Möller, Peter, Barth, Thomas F.E., Marienfeld, Ralf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Neoplasia Press 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190489/
https://www.ncbi.nlm.nih.gov/pubmed/34102454
http://dx.doi.org/10.1016/j.neo.2021.05.005
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author Müller, Sarah
Mayer, Stefanie
Möller, Peter
Barth, Thomas F.E.
Marienfeld, Ralf
author_facet Müller, Sarah
Mayer, Stefanie
Möller, Peter
Barth, Thomas F.E.
Marienfeld, Ralf
author_sort Müller, Sarah
collection PubMed
description The most prevalent histological type of non-small cell lung cancer (NSCLC) is adenocarcinoma. The WHO classifies this tumor into subtypes according to the predominant growth pattern such as lepidic, acinar, papillary, solid or micropapillary, each harboring specific molecular features. NSCLC adenocarcinoma heterogeneity is discussed to be a reason for therapy failure using targeted therapy or immune checkpoint inhibitors. For successful therapy of immune checkpoint inhibitors the expression and distribution of the involved immune checkpoint proteins is essential. Therefore, we aimed to investigate the distribution of five prominent immune checkpoint proteins in regard of the histological growth patterns of lung adenocarcinoma. We performed immunohistochemical staining of 84 tumor segments from 22 resected tumor samples to evaluate the expression of PD-L1, PD-1, Nectin-2, PVR, and TIGIT in distinct growth patterns of lung adenocarcinoma. We determined a distinct heterogeneity between and within different tumor segments regarding morphological growth patterns. Furthermore, expression of immune checkpoint proteins varied between different growth pattern areas as well as within one distinct growth pattern. Expression of PVR was significantly higher in solid compared to acinar growth pattern (p= 0.00736). Of note, we detected TIGIT not only on tumor infiltrating lymphocytes but also on tumor cells, whereas non-neoplastic lung tissue was consistently TIGIT-negative. The immune checkpoint protein distribution in histologic subtypes of pulmonary adenocarcinoma displays an considerable intra- and intertumoral heterogeneity implying the requirement of either a multiregion or an adjusted analysis when determining the expression status of PD-1:PD-L1 and the TIGIT:PVR/Nectin-2 checkpoint proteins as predictive markers.
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spelling pubmed-81904892021-06-23 Spatial distribution of immune checkpoint proteins in histological subtypes of lung adenocarcinoma Müller, Sarah Mayer, Stefanie Möller, Peter Barth, Thomas F.E. Marienfeld, Ralf Neoplasia Original Research The most prevalent histological type of non-small cell lung cancer (NSCLC) is adenocarcinoma. The WHO classifies this tumor into subtypes according to the predominant growth pattern such as lepidic, acinar, papillary, solid or micropapillary, each harboring specific molecular features. NSCLC adenocarcinoma heterogeneity is discussed to be a reason for therapy failure using targeted therapy or immune checkpoint inhibitors. For successful therapy of immune checkpoint inhibitors the expression and distribution of the involved immune checkpoint proteins is essential. Therefore, we aimed to investigate the distribution of five prominent immune checkpoint proteins in regard of the histological growth patterns of lung adenocarcinoma. We performed immunohistochemical staining of 84 tumor segments from 22 resected tumor samples to evaluate the expression of PD-L1, PD-1, Nectin-2, PVR, and TIGIT in distinct growth patterns of lung adenocarcinoma. We determined a distinct heterogeneity between and within different tumor segments regarding morphological growth patterns. Furthermore, expression of immune checkpoint proteins varied between different growth pattern areas as well as within one distinct growth pattern. Expression of PVR was significantly higher in solid compared to acinar growth pattern (p= 0.00736). Of note, we detected TIGIT not only on tumor infiltrating lymphocytes but also on tumor cells, whereas non-neoplastic lung tissue was consistently TIGIT-negative. The immune checkpoint protein distribution in histologic subtypes of pulmonary adenocarcinoma displays an considerable intra- and intertumoral heterogeneity implying the requirement of either a multiregion or an adjusted analysis when determining the expression status of PD-1:PD-L1 and the TIGIT:PVR/Nectin-2 checkpoint proteins as predictive markers. Neoplasia Press 2021-06-05 /pmc/articles/PMC8190489/ /pubmed/34102454 http://dx.doi.org/10.1016/j.neo.2021.05.005 Text en © 2021 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Original Research
Müller, Sarah
Mayer, Stefanie
Möller, Peter
Barth, Thomas F.E.
Marienfeld, Ralf
Spatial distribution of immune checkpoint proteins in histological subtypes of lung adenocarcinoma
title Spatial distribution of immune checkpoint proteins in histological subtypes of lung adenocarcinoma
title_full Spatial distribution of immune checkpoint proteins in histological subtypes of lung adenocarcinoma
title_fullStr Spatial distribution of immune checkpoint proteins in histological subtypes of lung adenocarcinoma
title_full_unstemmed Spatial distribution of immune checkpoint proteins in histological subtypes of lung adenocarcinoma
title_short Spatial distribution of immune checkpoint proteins in histological subtypes of lung adenocarcinoma
title_sort spatial distribution of immune checkpoint proteins in histological subtypes of lung adenocarcinoma
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8190489/
https://www.ncbi.nlm.nih.gov/pubmed/34102454
http://dx.doi.org/10.1016/j.neo.2021.05.005
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