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Research
Daniel Franzen
UniversitatsSpital Zurich
Corresponding Author
ORCiD: https://orcid.org/0000-0001-6080-9555
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Background
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 parallel cohort study was to investigate cytokines in serum and bronchoalveolar lavage fluid (BALF) expressed in patients with ICI-associated pneumonitis compared to healthy individuals.
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) and included in this parallel cohort study. Additionally, 12 healthy subjects from the biobank served as matched control group. 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 2017-02307 and 2018-01724).
Results
Absolute number and percentage of lymphocytes in BALF of patients with ICIaP were significantly higher compared to control group. For the investigated cytokines in serum and BALF, a significant increase of IL-6 levels was shown for patients with ICIaP (p=0.044, 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.
Keywords
Immune-checkpoint inhibitor associated pneumonitis, bronchoalveolar lavage, cytokine profile, interleukin 6
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A new preprint design is coming!
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This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Research
Daniel Franzen
UniversitatsSpital Zurich
Corresponding Author
ORCiD: https://orcid.org/0000-0001-6080-9555
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
History
CURRENT STATUS: Posted
Version 1
Posted 18 Dec, 2020
No community comments so far
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Pulmonology
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background
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 parallel cohort study was to investigate cytokines in serum and bronchoalveolar lavage fluid (BALF) expressed in patients with ICI-associated pneumonitis compared to healthy individuals.
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) and included in this parallel cohort study. Additionally, 12 healthy subjects from the biobank served as matched control group. 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 2017-02307 and 2018-01724).
Results
Absolute number and percentage of lymphocytes in BALF of patients with ICIaP were significantly higher compared to control group. For the investigated cytokines in serum and BALF, a significant increase of IL-6 levels was shown for patients with ICIaP (p=0.044, 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.
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