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Lung adenocarcinoma patients with malignant pleural effusions in hot adaptive immunity status have a longer overall survival

Malignant pleural effusion (MPE) is a common complication of lung adenocarcinoma (LADC) which is associated with a dismal prognosis. We investigated the prognostic role of PD-L1 and other immunomodulators expression in the immune compartment of MPE immune composition. MPE cytologic cell blocks of 83...

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Autores principales: Wu, Cheng-Guang, Casanova, Ruben, Mairinger, Fabian, Soltermann, Alex
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9577289/
https://www.ncbi.nlm.nih.gov/pubmed/36267973
http://dx.doi.org/10.3389/fonc.2022.1031094
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author Wu, Cheng-Guang
Casanova, Ruben
Mairinger, Fabian
Soltermann, Alex
author_facet Wu, Cheng-Guang
Casanova, Ruben
Mairinger, Fabian
Soltermann, Alex
author_sort Wu, Cheng-Guang
collection PubMed
description Malignant pleural effusion (MPE) is a common complication of lung adenocarcinoma (LADC) which is associated with a dismal prognosis. We investigated the prognostic role of PD-L1 and other immunomodulators expression in the immune compartment of MPE immune composition. MPE cytologic cell blocks of 83 LADC patients were analysed for the mRNA expression of 770 cancer-immune genes by the NanoString nCounter platform. The expression of relevant immune cell lineage markers was validated by immunohistochemistry (IHC) using quantitative pathology. The mRNA immune profiling identified four MPE patient clusters (C). C1/2 (adaptive+, hot) showed better overall survival (OS) than C3/4 (adaptive-, cold). Additionally, cold immunity profiles (adaptive-), C4 (innate+) were associated with worse OS than C3 (innate-). High PD-L1 expression was linked to the regulation of T cell activation and interferon signalling pathways. Genes of pattern recognition receptor and type I interferon signalling pathways were specifically upregulated in the long-survival (≥90 days) patient group. Moreover, immunomodulators were co-activated and highly expressed in hot adaptive immunity patient clusters, whereas CD274 (PD-L1), TNFRSF9 (4-1BB), VEGFA (VEGF-A) and CD276 (B7-H3) were upregulated in the groups referred as cold. The patient cluster, age and PD-L1 expression were independent prognosticators for LADC MPE patients (p-value < 0.05). Our study sheds light on the variances of immune contexture regarding different PD-L1 expression and survival conditions. It revealed four distinct prognostic patient clusters with specific immune cell components and immunomodulator expression profiles, which, collectively, is supportive for future therapeutic and prognosis for cancer management.
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spelling pubmed-95772892022-10-19 Lung adenocarcinoma patients with malignant pleural effusions in hot adaptive immunity status have a longer overall survival Wu, Cheng-Guang Casanova, Ruben Mairinger, Fabian Soltermann, Alex Front Oncol Oncology Malignant pleural effusion (MPE) is a common complication of lung adenocarcinoma (LADC) which is associated with a dismal prognosis. We investigated the prognostic role of PD-L1 and other immunomodulators expression in the immune compartment of MPE immune composition. MPE cytologic cell blocks of 83 LADC patients were analysed for the mRNA expression of 770 cancer-immune genes by the NanoString nCounter platform. The expression of relevant immune cell lineage markers was validated by immunohistochemistry (IHC) using quantitative pathology. The mRNA immune profiling identified four MPE patient clusters (C). C1/2 (adaptive+, hot) showed better overall survival (OS) than C3/4 (adaptive-, cold). Additionally, cold immunity profiles (adaptive-), C4 (innate+) were associated with worse OS than C3 (innate-). High PD-L1 expression was linked to the regulation of T cell activation and interferon signalling pathways. Genes of pattern recognition receptor and type I interferon signalling pathways were specifically upregulated in the long-survival (≥90 days) patient group. Moreover, immunomodulators were co-activated and highly expressed in hot adaptive immunity patient clusters, whereas CD274 (PD-L1), TNFRSF9 (4-1BB), VEGFA (VEGF-A) and CD276 (B7-H3) were upregulated in the groups referred as cold. The patient cluster, age and PD-L1 expression were independent prognosticators for LADC MPE patients (p-value < 0.05). Our study sheds light on the variances of immune contexture regarding different PD-L1 expression and survival conditions. It revealed four distinct prognostic patient clusters with specific immune cell components and immunomodulator expression profiles, which, collectively, is supportive for future therapeutic and prognosis for cancer management. Frontiers Media S.A. 2022-10-04 /pmc/articles/PMC9577289/ /pubmed/36267973 http://dx.doi.org/10.3389/fonc.2022.1031094 Text en Copyright © 2022 Wu, Casanova, Mairinger and Soltermann https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Wu, Cheng-Guang
Casanova, Ruben
Mairinger, Fabian
Soltermann, Alex
Lung adenocarcinoma patients with malignant pleural effusions in hot adaptive immunity status have a longer overall survival
title Lung adenocarcinoma patients with malignant pleural effusions in hot adaptive immunity status have a longer overall survival
title_full Lung adenocarcinoma patients with malignant pleural effusions in hot adaptive immunity status have a longer overall survival
title_fullStr Lung adenocarcinoma patients with malignant pleural effusions in hot adaptive immunity status have a longer overall survival
title_full_unstemmed Lung adenocarcinoma patients with malignant pleural effusions in hot adaptive immunity status have a longer overall survival
title_short Lung adenocarcinoma patients with malignant pleural effusions in hot adaptive immunity status have a longer overall survival
title_sort lung adenocarcinoma patients with malignant pleural effusions in hot adaptive immunity status have a longer overall survival
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9577289/
https://www.ncbi.nlm.nih.gov/pubmed/36267973
http://dx.doi.org/10.3389/fonc.2022.1031094
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