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Improved Prognostic Prediction in Never-Smoker Lung Cancer Patients by Integration of a Systemic Inflammation Marker with Tumor Immune Contexture Analysis

Almost 25% of lung cancers (LCs) occur in never-smokers. LC inflammatory profile, based on plasma C-reactive protein levels (CRP), predicts mortality, independently by smoking-status. We hypothesized that: CRP could be associated with tumor immune contexture (TIC) in never-smokers and both these two...

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Autores principales: Milione, Massimo, Boeri, Mattia, Cantarutti, Anna, Centonze, Giovanni, Busico, Adele, Suatoni, Paola, Garzone, Giovanna, Cattaneo, Laura, Tamborini, Elena, Perrone, Federica, Mangogna, Alessandro, Corrao, Giovanni, Pruneri, Giancarlo, Sozzi, Gabriella, Anichini, Andrea, Pastorino, Ugo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408913/
https://www.ncbi.nlm.nih.gov/pubmed/32646072
http://dx.doi.org/10.3390/cancers12071828
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author Milione, Massimo
Boeri, Mattia
Cantarutti, Anna
Centonze, Giovanni
Busico, Adele
Suatoni, Paola
Garzone, Giovanna
Cattaneo, Laura
Tamborini, Elena
Perrone, Federica
Mangogna, Alessandro
Corrao, Giovanni
Pruneri, Giancarlo
Sozzi, Gabriella
Anichini, Andrea
Pastorino, Ugo
author_facet Milione, Massimo
Boeri, Mattia
Cantarutti, Anna
Centonze, Giovanni
Busico, Adele
Suatoni, Paola
Garzone, Giovanna
Cattaneo, Laura
Tamborini, Elena
Perrone, Federica
Mangogna, Alessandro
Corrao, Giovanni
Pruneri, Giancarlo
Sozzi, Gabriella
Anichini, Andrea
Pastorino, Ugo
author_sort Milione, Massimo
collection PubMed
description Almost 25% of lung cancers (LCs) occur in never-smokers. LC inflammatory profile, based on plasma C-reactive protein levels (CRP), predicts mortality, independently by smoking-status. We hypothesized that: CRP could be associated with tumor immune contexture (TIC) in never-smokers and both these two parameters may improve their prognosis. Sixty-eight never-smokers LC patients with high or low CRP were selected. The programmed cell death protein 1 (PD-1) and its ligand (PD-L1), the human leukocyte antigens (HLA-DR and HLA-I), CD8, CD4, CD3, CD33, CD163, and CD68 were evaluated by immunohistochemistry on surgical samples given TIC evaluation. The classification model based on TIC scores was generated by Classification and Regression Tree analysis. Tumor mutational burden was evaluated by targeted next-generation sequencing. Exclusively high CRP (H-CRP) subset showed PD-L1 expression in 35% of LC as well as lower HLA-I and HLA-DR in their stromal cells. CD3, CD4, CD8, HLA-I, HLA-DR tumor cells staining were associated with a “low inflammatory profile” subset. CRP and LC immune profiles drive clinical outcome: 5-year survival 88% against 8% was associated with low and high-risk profiles (p < 0.0001). Clinical outcome prediction in never-smoker LC patients may be improved by both CRP and tumor immune contexture evaluation.
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spelling pubmed-74089132020-08-13 Improved Prognostic Prediction in Never-Smoker Lung Cancer Patients by Integration of a Systemic Inflammation Marker with Tumor Immune Contexture Analysis Milione, Massimo Boeri, Mattia Cantarutti, Anna Centonze, Giovanni Busico, Adele Suatoni, Paola Garzone, Giovanna Cattaneo, Laura Tamborini, Elena Perrone, Federica Mangogna, Alessandro Corrao, Giovanni Pruneri, Giancarlo Sozzi, Gabriella Anichini, Andrea Pastorino, Ugo Cancers (Basel) Article Almost 25% of lung cancers (LCs) occur in never-smokers. LC inflammatory profile, based on plasma C-reactive protein levels (CRP), predicts mortality, independently by smoking-status. We hypothesized that: CRP could be associated with tumor immune contexture (TIC) in never-smokers and both these two parameters may improve their prognosis. Sixty-eight never-smokers LC patients with high or low CRP were selected. The programmed cell death protein 1 (PD-1) and its ligand (PD-L1), the human leukocyte antigens (HLA-DR and HLA-I), CD8, CD4, CD3, CD33, CD163, and CD68 were evaluated by immunohistochemistry on surgical samples given TIC evaluation. The classification model based on TIC scores was generated by Classification and Regression Tree analysis. Tumor mutational burden was evaluated by targeted next-generation sequencing. Exclusively high CRP (H-CRP) subset showed PD-L1 expression in 35% of LC as well as lower HLA-I and HLA-DR in their stromal cells. CD3, CD4, CD8, HLA-I, HLA-DR tumor cells staining were associated with a “low inflammatory profile” subset. CRP and LC immune profiles drive clinical outcome: 5-year survival 88% against 8% was associated with low and high-risk profiles (p < 0.0001). Clinical outcome prediction in never-smoker LC patients may be improved by both CRP and tumor immune contexture evaluation. MDPI 2020-07-07 /pmc/articles/PMC7408913/ /pubmed/32646072 http://dx.doi.org/10.3390/cancers12071828 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Milione, Massimo
Boeri, Mattia
Cantarutti, Anna
Centonze, Giovanni
Busico, Adele
Suatoni, Paola
Garzone, Giovanna
Cattaneo, Laura
Tamborini, Elena
Perrone, Federica
Mangogna, Alessandro
Corrao, Giovanni
Pruneri, Giancarlo
Sozzi, Gabriella
Anichini, Andrea
Pastorino, Ugo
Improved Prognostic Prediction in Never-Smoker Lung Cancer Patients by Integration of a Systemic Inflammation Marker with Tumor Immune Contexture Analysis
title Improved Prognostic Prediction in Never-Smoker Lung Cancer Patients by Integration of a Systemic Inflammation Marker with Tumor Immune Contexture Analysis
title_full Improved Prognostic Prediction in Never-Smoker Lung Cancer Patients by Integration of a Systemic Inflammation Marker with Tumor Immune Contexture Analysis
title_fullStr Improved Prognostic Prediction in Never-Smoker Lung Cancer Patients by Integration of a Systemic Inflammation Marker with Tumor Immune Contexture Analysis
title_full_unstemmed Improved Prognostic Prediction in Never-Smoker Lung Cancer Patients by Integration of a Systemic Inflammation Marker with Tumor Immune Contexture Analysis
title_short Improved Prognostic Prediction in Never-Smoker Lung Cancer Patients by Integration of a Systemic Inflammation Marker with Tumor Immune Contexture Analysis
title_sort improved prognostic prediction in never-smoker lung cancer patients by integration of a systemic inflammation marker with tumor immune contexture analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7408913/
https://www.ncbi.nlm.nih.gov/pubmed/32646072
http://dx.doi.org/10.3390/cancers12071828
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