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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2021
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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. |
format | Online Article Text |
id | pubmed-8190489 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
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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