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      Cytokine profile of bronchoalveolar lavage in patients with and without checkpoint inhibitor pneumonitis

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          Abstract

          Background

          Checkpoint inhibitor pneumonitis (CIP) that develops following immune checkpoint inhibitor (ICI) treatment can be difficult to distinguish from other common etiologies of lung inflammation in cancer patients. Here, we evaluate the bronchoalveolar lavage fluid (BAL) for potential biomarkers specific to CIP.

          Methods

          We conducted a retrospective study of patients who underwent standard of care bronchoscopy to compare the cytokines of interest between patients with and without CIP and with and without immune-mediated pulmonary diseases. Pulmonary diagnoses were determined by the treating clinician at the time of bronchoscopy and retroactively reviewed for agreement by the study team.

          Results

          Thirty-seven patients were included, and 24 (64.9%) had pulmonary infection, 2 (5.4%) had pulmonary edema, 6 (16.2%) had non-CIP drug-induced pneumonitis, 3 (8.1%) had CIP, 5 (13.5%) had immune-mediated ILD or autoimmune vasculitis, 4 (10.8%) had cancer progression, and 4 (10.8%) had nonimmune-mediated interstitial lung disease (ILD). IL-6 from the BAL was significantly higher in patients with CIP compared to those with cancer progression and nonimmune-mediated ILD, and IL-6 was significantly higher in patients with immune-mediated pulmonary diseases compared to cancer progression, nonimmune-mediated ILD, and infection.

          Conclusions

          BAL IL-6 distinguished CIP from other common, important causes of pulmonary infiltrates in patients with cancer, suggesting it may give insight into the pathophysiology of CIP and has potential as a biomarker.

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          Most cited references19

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          Previous trials showed promising antitumor activity and an acceptable safety profile associated with pembrolizumab in patients with early triple-negative breast cancer. Whether the addition of pembrolizumab to neoadjuvant chemotherapy would significantly increase the percentage of patients with early triple-negative breast cancer who have a pathological complete response (defined as no invasive cancer in the breast and negative nodes) at definitive surgery is unclear.
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              Immune checkpoint inhibitors are poised to revolutionize the management of a growing number of malignancies. Unfortunately, the management of steroid-refractory immune mediated adverse events is based on a paucity of randomized data and limited to single center experiences. Our initial experience with the IL-6 receptor antagonist tocilizumab showed clinical improvement in a wide variety of irAEs. As a result, we adopted the use of tocilizumab for the management of steroid refractory irAEs.

                Author and article information

                Contributors
                kevin.ho@osumc.edu
                Journal
                Cancer Immunol Immunother
                Cancer Immunol Immunother
                Cancer Immunology, Immunotherapy : CII
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0340-7004
                1432-0851
                3 January 2025
                3 January 2025
                February 2025
                : 74
                : 2
                : 46
                Affiliations
                [1 ]Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, ( https://ror.org/00c01js51) 241 W 11th Ave, Suite 5000, Columbus, OH 43201 USA
                [2 ]Center for Biostatistics, The Ohio State University-James Comprehensive Cancer Center, ( https://ror.org/028t46f04) Columbus, OH USA
                [3 ]Division of Rheumatology, Department of Internal Medicine, The Ohio State University Wexner Medical Center, ( https://ror.org/00c01js51) Columbus, OH USA
                [4 ]Division of Medical Oncology, Department of Internal Medicine, The Ohio State University-James Comprehensive Cancer Center, ( https://ror.org/028t46f04) Columbus, OH USA
                Article
                3902
                10.1007/s00262-024-03902-3
                11699005
                39751662
                66fa6c9f-191e-4136-882e-47b9c8f565fc
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, 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 you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. 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-nc-nd/4.0/.

                History
                : 25 September 2024
                : 20 November 2024
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100006108, National Center for Advancing Translational Sciences;
                Award ID: UL1TR002733
                Award Recipient :
                Categories
                Brief Report
                Custom metadata
                © Springer-Verlag GmbH Germany, part of Springer Nature 2025

                Oncology & Radiotherapy
                immune checkpoint inhibitor pneumonitis,cancer,immunotherapy
                Oncology & Radiotherapy
                immune checkpoint inhibitor pneumonitis, cancer, immunotherapy

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