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Expression of immune checkpoint PD-1 in non-small cell lung cancer is associated with tumor cell DNA-dependent protein kinase

Immunotherapy using immune checkpoint inhibitors has demonstrated durable responses and has significantly improved survival in patients with non-small cell lung cancer (NSCLC). Moreover, immunotherapy is increasingly used in combination with cytotoxic treatments such as chemotherapy and radiotherapy...

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Autores principales: Saar, Marika, Narits, Jaanika, Mägi, Laura, Aaspõllu, Hardi, Vapper, Annett, Kase, Marju, Minajeva, Ave, Vooder, Tõnu, Tamm, Hannes, Buldakov, Maksim, Lavõgina, Darja, Jaal, Jana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375025/
https://www.ncbi.nlm.nih.gov/pubmed/34462666
http://dx.doi.org/10.3892/mco.2021.2369
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author Saar, Marika
Narits, Jaanika
Mägi, Laura
Aaspõllu, Hardi
Vapper, Annett
Kase, Marju
Minajeva, Ave
Vooder, Tõnu
Tamm, Hannes
Buldakov, Maksim
Lavõgina, Darja
Jaal, Jana
author_facet Saar, Marika
Narits, Jaanika
Mägi, Laura
Aaspõllu, Hardi
Vapper, Annett
Kase, Marju
Minajeva, Ave
Vooder, Tõnu
Tamm, Hannes
Buldakov, Maksim
Lavõgina, Darja
Jaal, Jana
author_sort Saar, Marika
collection PubMed
description Immunotherapy using immune checkpoint inhibitors has demonstrated durable responses and has significantly improved survival in patients with non-small cell lung cancer (NSCLC). Moreover, immunotherapy is increasingly used in combination with cytotoxic treatments such as chemotherapy and radiotherapy. Although the combined treatments are more effective, the underling mechanisms that lead to higher antitumor activity are not fully understood. Therefore, the aim of the current retrospective study was to determine the relationship between expression of immune checkpoints [programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1)] and the enzyme DNA-dependent protein kinase (DNA-PK), which is part of a key pathway involved in the repair of cytotoxic cancer therapy induced damage. Surgically excised NSCLC tissues (n=121) were histologically examined for overall extent of inflammation (score 0-3). Expression levels of PD-1 (number of PD-1 positive cells), PD-L1 [tumor proportion score (TPS); %] and DNA-PK (proportion of DNA-PK positive tumor cells; %) were determined using immunohistochemistry. Expressions of these markers were compared in different clinicopathological subgroups and later used for nonparametric Spearman correlation analysis to determine associations. In patients with NSCLC, PD-1 was significantly expressed in males (P=0.030) and in patients with no or trivial inflammation scores (P=0.030). PD-L1 expression was also significantly higher in current smokers (P=0.025). Correlation analysis was based on the individual values of patients and revealed a significant association between one of the targets of immune checkpoint inhibitors and tumor cell DNA-PK. Tumors with higher numbers of PD-1 positive cells also demonstrated higher tumor cell DNA-PK expressions (P=0.027). The results demonstrated a significant positive correlation between the PD-1/PD-L1 axis and tumor cell DNA-PK expression in patients with NSCLC. Further studies are required to clarify the significance of this correlation and its effect on the efficacy of immunotherapy and cytotoxic cancer therapy combinations.
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spelling pubmed-83750252021-08-29 Expression of immune checkpoint PD-1 in non-small cell lung cancer is associated with tumor cell DNA-dependent protein kinase Saar, Marika Narits, Jaanika Mägi, Laura Aaspõllu, Hardi Vapper, Annett Kase, Marju Minajeva, Ave Vooder, Tõnu Tamm, Hannes Buldakov, Maksim Lavõgina, Darja Jaal, Jana Mol Clin Oncol Articles Immunotherapy using immune checkpoint inhibitors has demonstrated durable responses and has significantly improved survival in patients with non-small cell lung cancer (NSCLC). Moreover, immunotherapy is increasingly used in combination with cytotoxic treatments such as chemotherapy and radiotherapy. Although the combined treatments are more effective, the underling mechanisms that lead to higher antitumor activity are not fully understood. Therefore, the aim of the current retrospective study was to determine the relationship between expression of immune checkpoints [programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1)] and the enzyme DNA-dependent protein kinase (DNA-PK), which is part of a key pathway involved in the repair of cytotoxic cancer therapy induced damage. Surgically excised NSCLC tissues (n=121) were histologically examined for overall extent of inflammation (score 0-3). Expression levels of PD-1 (number of PD-1 positive cells), PD-L1 [tumor proportion score (TPS); %] and DNA-PK (proportion of DNA-PK positive tumor cells; %) were determined using immunohistochemistry. Expressions of these markers were compared in different clinicopathological subgroups and later used for nonparametric Spearman correlation analysis to determine associations. In patients with NSCLC, PD-1 was significantly expressed in males (P=0.030) and in patients with no or trivial inflammation scores (P=0.030). PD-L1 expression was also significantly higher in current smokers (P=0.025). Correlation analysis was based on the individual values of patients and revealed a significant association between one of the targets of immune checkpoint inhibitors and tumor cell DNA-PK. Tumors with higher numbers of PD-1 positive cells also demonstrated higher tumor cell DNA-PK expressions (P=0.027). The results demonstrated a significant positive correlation between the PD-1/PD-L1 axis and tumor cell DNA-PK expression in patients with NSCLC. Further studies are required to clarify the significance of this correlation and its effect on the efficacy of immunotherapy and cytotoxic cancer therapy combinations. D.A. Spandidos 2021-10 2021-08-10 /pmc/articles/PMC8375025/ /pubmed/34462666 http://dx.doi.org/10.3892/mco.2021.2369 Text en Copyright: © Saar et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Saar, Marika
Narits, Jaanika
Mägi, Laura
Aaspõllu, Hardi
Vapper, Annett
Kase, Marju
Minajeva, Ave
Vooder, Tõnu
Tamm, Hannes
Buldakov, Maksim
Lavõgina, Darja
Jaal, Jana
Expression of immune checkpoint PD-1 in non-small cell lung cancer is associated with tumor cell DNA-dependent protein kinase
title Expression of immune checkpoint PD-1 in non-small cell lung cancer is associated with tumor cell DNA-dependent protein kinase
title_full Expression of immune checkpoint PD-1 in non-small cell lung cancer is associated with tumor cell DNA-dependent protein kinase
title_fullStr Expression of immune checkpoint PD-1 in non-small cell lung cancer is associated with tumor cell DNA-dependent protein kinase
title_full_unstemmed Expression of immune checkpoint PD-1 in non-small cell lung cancer is associated with tumor cell DNA-dependent protein kinase
title_short Expression of immune checkpoint PD-1 in non-small cell lung cancer is associated with tumor cell DNA-dependent protein kinase
title_sort expression of immune checkpoint pd-1 in non-small cell lung cancer is associated with tumor cell dna-dependent protein kinase
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375025/
https://www.ncbi.nlm.nih.gov/pubmed/34462666
http://dx.doi.org/10.3892/mco.2021.2369
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