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Protein Profiling of Breast Carcinomas Reveals Expression of Immune-Suppressive Factors and Signatures Relevant for Patient Outcome

SIMPLE SUMMARY: Breast cancer treatment has improved substantially over the last decade. Still, the failure of treatment and therapy resistance are urgent problems. Here, we assessed cellular signaling within primary cancer tissue to evaluate the possibility of developing strategies that lead to bet...

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Autores principales: Ruoff, Felix, Kersten, Nicolas, Anderle, Nicole, Jerbi, Sandra, Stahl, Aaron, Koch, André, Staebler, Annette, Hartkopf, Andreas, Brucker, Sara Y., Hahn, Markus, Schenke-Layland, Katja, Schmees, Christian, Templin, Markus F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496820/
https://www.ncbi.nlm.nih.gov/pubmed/36139700
http://dx.doi.org/10.3390/cancers14184542
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author Ruoff, Felix
Kersten, Nicolas
Anderle, Nicole
Jerbi, Sandra
Stahl, Aaron
Koch, André
Staebler, Annette
Hartkopf, Andreas
Brucker, Sara Y.
Hahn, Markus
Schenke-Layland, Katja
Schmees, Christian
Templin, Markus F.
author_facet Ruoff, Felix
Kersten, Nicolas
Anderle, Nicole
Jerbi, Sandra
Stahl, Aaron
Koch, André
Staebler, Annette
Hartkopf, Andreas
Brucker, Sara Y.
Hahn, Markus
Schenke-Layland, Katja
Schmees, Christian
Templin, Markus F.
author_sort Ruoff, Felix
collection PubMed
description SIMPLE SUMMARY: Breast cancer treatment has improved substantially over the last decade. Still, the failure of treatment and therapy resistance are urgent problems. Here, we assessed cellular signaling within primary cancer tissue to evaluate the possibility of developing strategies that lead to better patient stratification and the development of personalized treatment options. By employing DigiWest technology, the expression and activation of the regulators of key signaling pathways in breast cancer tissue were monitored. A positive correlation between immune cell infiltration and event-free survival was detected. PPARγ activation showed a negative correlation with immune cell infiltration, suggesting a novel immune evasion mechanism. ABSTRACT: In cancer, the complex interplay between tumor cells and the tumor microenvironment results in the modulation of signaling processes. By assessing the expression of a multitude of proteins and protein variants in cancer tissue, wide-ranging information on signaling pathway activation and the status of the immunological landscape is obtainable and may provide viable information on the treatment response. Archived breast cancer tissues from a cohort of 84 patients (no adjuvant therapy) were analyzed by high-throughput Western blotting, and the expression of 150 proteins covering central cancer pathways and immune cell markers was examined. By assessing CD8α, CD11c, CD16 and CD68 expression, immune cell infiltration was determined and revealed a strong correlation between event-free patient survival and the infiltration of immune cells. The presence of tumor-infiltrating lymphocytes was linked to the pronounced activation of the Jak/Stat signaling pathway and apoptotic processes. The elevated phosphorylation of PPARγ (pS112) in non-immune-infiltrated tumors suggests a novel immune evasion mechanism in breast cancer characterized by increased PPARγ phosphorylation. Multiplexed immune cell marker assessment and the protein profiling of tumor tissue provide functional signaling data facilitating breast cancer patient stratification.
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spelling pubmed-94968202022-09-23 Protein Profiling of Breast Carcinomas Reveals Expression of Immune-Suppressive Factors and Signatures Relevant for Patient Outcome Ruoff, Felix Kersten, Nicolas Anderle, Nicole Jerbi, Sandra Stahl, Aaron Koch, André Staebler, Annette Hartkopf, Andreas Brucker, Sara Y. Hahn, Markus Schenke-Layland, Katja Schmees, Christian Templin, Markus F. Cancers (Basel) Article SIMPLE SUMMARY: Breast cancer treatment has improved substantially over the last decade. Still, the failure of treatment and therapy resistance are urgent problems. Here, we assessed cellular signaling within primary cancer tissue to evaluate the possibility of developing strategies that lead to better patient stratification and the development of personalized treatment options. By employing DigiWest technology, the expression and activation of the regulators of key signaling pathways in breast cancer tissue were monitored. A positive correlation between immune cell infiltration and event-free survival was detected. PPARγ activation showed a negative correlation with immune cell infiltration, suggesting a novel immune evasion mechanism. ABSTRACT: In cancer, the complex interplay between tumor cells and the tumor microenvironment results in the modulation of signaling processes. By assessing the expression of a multitude of proteins and protein variants in cancer tissue, wide-ranging information on signaling pathway activation and the status of the immunological landscape is obtainable and may provide viable information on the treatment response. Archived breast cancer tissues from a cohort of 84 patients (no adjuvant therapy) were analyzed by high-throughput Western blotting, and the expression of 150 proteins covering central cancer pathways and immune cell markers was examined. By assessing CD8α, CD11c, CD16 and CD68 expression, immune cell infiltration was determined and revealed a strong correlation between event-free patient survival and the infiltration of immune cells. The presence of tumor-infiltrating lymphocytes was linked to the pronounced activation of the Jak/Stat signaling pathway and apoptotic processes. The elevated phosphorylation of PPARγ (pS112) in non-immune-infiltrated tumors suggests a novel immune evasion mechanism in breast cancer characterized by increased PPARγ phosphorylation. Multiplexed immune cell marker assessment and the protein profiling of tumor tissue provide functional signaling data facilitating breast cancer patient stratification. MDPI 2022-09-19 /pmc/articles/PMC9496820/ /pubmed/36139700 http://dx.doi.org/10.3390/cancers14184542 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ruoff, Felix
Kersten, Nicolas
Anderle, Nicole
Jerbi, Sandra
Stahl, Aaron
Koch, André
Staebler, Annette
Hartkopf, Andreas
Brucker, Sara Y.
Hahn, Markus
Schenke-Layland, Katja
Schmees, Christian
Templin, Markus F.
Protein Profiling of Breast Carcinomas Reveals Expression of Immune-Suppressive Factors and Signatures Relevant for Patient Outcome
title Protein Profiling of Breast Carcinomas Reveals Expression of Immune-Suppressive Factors and Signatures Relevant for Patient Outcome
title_full Protein Profiling of Breast Carcinomas Reveals Expression of Immune-Suppressive Factors and Signatures Relevant for Patient Outcome
title_fullStr Protein Profiling of Breast Carcinomas Reveals Expression of Immune-Suppressive Factors and Signatures Relevant for Patient Outcome
title_full_unstemmed Protein Profiling of Breast Carcinomas Reveals Expression of Immune-Suppressive Factors and Signatures Relevant for Patient Outcome
title_short Protein Profiling of Breast Carcinomas Reveals Expression of Immune-Suppressive Factors and Signatures Relevant for Patient Outcome
title_sort protein profiling of breast carcinomas reveals expression of immune-suppressive factors and signatures relevant for patient outcome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9496820/
https://www.ncbi.nlm.nih.gov/pubmed/36139700
http://dx.doi.org/10.3390/cancers14184542
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