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Analysis of cytokines in serum and bronchoalveolar lavage fluid in patients with immune-checkpoint inhibitor-associated pneumonitis: a cross-sectional case–control study
PURPOSE: Immune-checkpoint inhibitors (ICI) present a new treatment for malignancies by boosting the immune system. This has led to a variety of immune-related adverse events, including ICI-associated pneumonitis (ICIaP). Diagnosis thereof is often challenging, and its pathogenesis has not yet been...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189083/ https://www.ncbi.nlm.nih.gov/pubmed/34347128 http://dx.doi.org/10.1007/s00432-021-03750-z |
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author | Kowalski, Benedikt Valaperti, Alan Bezel, Pascal Steiner, Urs C. Scholtze, Dieter Wieser, Stephan Vonow-Eisenring, Maya Widmer, Andrea Kohler, Malcolm Franzen, Daniel |
author_facet | Kowalski, Benedikt Valaperti, Alan Bezel, Pascal Steiner, Urs C. Scholtze, Dieter Wieser, Stephan Vonow-Eisenring, Maya Widmer, Andrea Kohler, Malcolm Franzen, Daniel |
author_sort | Kowalski, Benedikt |
collection | PubMed |
description | PURPOSE: Immune-checkpoint inhibitors (ICI) present a new treatment for malignancies by boosting the immune system. This has led to a variety of immune-related adverse events, including ICI-associated pneumonitis (ICIaP). Diagnosis thereof is often challenging, and its pathogenesis has not yet been fully understood. The aim of this cross-sectional case–control study was to investigate cytokines in serum and bronchoalveolar lavage fluid (BALF) expressed in patients with ICIaP compared to controls consisting of healthy individuals, patients with lung cancer and patients with interstitial lung diseases (ILD) other than ICIaP. METHODS: From January 2018 until June 2019, 401 adult patients with various lung diseases were prospectively enrolled in a BALF- and serum biobank, called BALOTHEK. Of these, 12 patients were diagnosed with ICIaP (Pembrolizumab, Ipilimumab, or both, and Durvalumab) serving as case group. Subjects with one of three diagnosis groups from BALOTHEK, including lung cancer, ILD other than ICIaP, and healthy individuals, served as matched controls. The following 11 cytokines were simultaneously analyzed in BALF and serum of each study participant: interferon gamma, tumor necrosis factor alpha, interleukin (IL) 1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-12p70, IL-13 and IL-17A. This study was approved by the local ethic review committee (BASEC-ID 2017-02,307 and 2018-01,724). RESULTS: Absolute number and percentage of lymphocytes in BALF of patients with ICIaP were significantly higher compared to control groups. For the investigated cytokines in BALF, a significant increase of IL-6 level was shown for patients with ICIaP compared to control groups (p = 0.031, adjusted for multiple comparisons). CONCLUSION: Cytokine profile assessed in BALF shows promising potential for facilitating diagnosis and understanding of pathophysiology of ICIaP. IL-6 may not only contribute to better understanding of pathophysiology but also herald therapeutic implications for Tocilizumab. |
format | Online Article Text |
id | pubmed-9189083 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-91890832022-06-14 Analysis of cytokines in serum and bronchoalveolar lavage fluid in patients with immune-checkpoint inhibitor-associated pneumonitis: a cross-sectional case–control study Kowalski, Benedikt Valaperti, Alan Bezel, Pascal Steiner, Urs C. Scholtze, Dieter Wieser, Stephan Vonow-Eisenring, Maya Widmer, Andrea Kohler, Malcolm Franzen, Daniel J Cancer Res Clin Oncol Original Article – Clinical Oncology PURPOSE: Immune-checkpoint inhibitors (ICI) present a new treatment for malignancies by boosting the immune system. This has led to a variety of immune-related adverse events, including ICI-associated pneumonitis (ICIaP). Diagnosis thereof is often challenging, and its pathogenesis has not yet been fully understood. The aim of this cross-sectional case–control study was to investigate cytokines in serum and bronchoalveolar lavage fluid (BALF) expressed in patients with ICIaP compared to controls consisting of healthy individuals, patients with lung cancer and patients with interstitial lung diseases (ILD) other than ICIaP. METHODS: From January 2018 until June 2019, 401 adult patients with various lung diseases were prospectively enrolled in a BALF- and serum biobank, called BALOTHEK. Of these, 12 patients were diagnosed with ICIaP (Pembrolizumab, Ipilimumab, or both, and Durvalumab) serving as case group. Subjects with one of three diagnosis groups from BALOTHEK, including lung cancer, ILD other than ICIaP, and healthy individuals, served as matched controls. The following 11 cytokines were simultaneously analyzed in BALF and serum of each study participant: interferon gamma, tumor necrosis factor alpha, interleukin (IL) 1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-12p70, IL-13 and IL-17A. This study was approved by the local ethic review committee (BASEC-ID 2017-02,307 and 2018-01,724). RESULTS: Absolute number and percentage of lymphocytes in BALF of patients with ICIaP were significantly higher compared to control groups. For the investigated cytokines in BALF, a significant increase of IL-6 level was shown for patients with ICIaP compared to control groups (p = 0.031, adjusted for multiple comparisons). CONCLUSION: Cytokine profile assessed in BALF shows promising potential for facilitating diagnosis and understanding of pathophysiology of ICIaP. IL-6 may not only contribute to better understanding of pathophysiology but also herald therapeutic implications for Tocilizumab. Springer Berlin Heidelberg 2021-08-04 2022 /pmc/articles/PMC9189083/ /pubmed/34347128 http://dx.doi.org/10.1007/s00432-021-03750-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article – Clinical Oncology Kowalski, Benedikt Valaperti, Alan Bezel, Pascal Steiner, Urs C. Scholtze, Dieter Wieser, Stephan Vonow-Eisenring, Maya Widmer, Andrea Kohler, Malcolm Franzen, Daniel Analysis of cytokines in serum and bronchoalveolar lavage fluid in patients with immune-checkpoint inhibitor-associated pneumonitis: a cross-sectional case–control study |
title | Analysis of cytokines in serum and bronchoalveolar lavage fluid in patients with immune-checkpoint inhibitor-associated pneumonitis: a cross-sectional case–control study |
title_full | Analysis of cytokines in serum and bronchoalveolar lavage fluid in patients with immune-checkpoint inhibitor-associated pneumonitis: a cross-sectional case–control study |
title_fullStr | Analysis of cytokines in serum and bronchoalveolar lavage fluid in patients with immune-checkpoint inhibitor-associated pneumonitis: a cross-sectional case–control study |
title_full_unstemmed | Analysis of cytokines in serum and bronchoalveolar lavage fluid in patients with immune-checkpoint inhibitor-associated pneumonitis: a cross-sectional case–control study |
title_short | Analysis of cytokines in serum and bronchoalveolar lavage fluid in patients with immune-checkpoint inhibitor-associated pneumonitis: a cross-sectional case–control study |
title_sort | analysis of cytokines in serum and bronchoalveolar lavage fluid in patients with immune-checkpoint inhibitor-associated pneumonitis: a cross-sectional case–control study |
topic | Original Article – Clinical Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9189083/ https://www.ncbi.nlm.nih.gov/pubmed/34347128 http://dx.doi.org/10.1007/s00432-021-03750-z |
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