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Background: Immune checkpoint inhibitor-related pneumonitis (CIP) stands out as a particularly severe adverse event caused by immune checkpoint inhibitors, with a substantial real-world incidence ranging from 13 to 19%. While systemic corticosteroids represent the standard treatment for CIP, therapeutic options become limited in cases where patients do not respond to corticosteroid therapy. Such patients are classified as having steroid-resistant CIP, often associated with a poor prognosis. This case study provides insight into the symptoms, diagnostic process, and treatment approach for steroid-resistant CIP. Notably, successful management is demonstrated through the utilization of cyclosporine, highlighting its potential mechanisms of action in effectively treating steroid-resistant CIP., Case Description: We present the case of a 53-year-old male with stage IV. A non-small cell lung cancer (NSCLC), who experienced elevated fever, cough, and dyspnea subsequent to immunotherapy treatment. Based on his medical history, clinical manifestations, and radiological findings, the patient was diagnosed with CIP. Initial administration of led to improvement, but during the subsequent tapering of corticosteroid therapy, a resurgence of CIP occurred, resulting in respiratory failure. Consequently, we arrived at the diagnosis of steroid-resistant CIP, prompting the implementation of a combination therapy with cyclosporine and corticosteroids to establish stable disease control. Upon systematic reduction of corticosteroid dosage, the patient maintained a favorable response with no recurrence., Conclusions: This marks the first instance of effectively managing steroid-resistant CIP through the combined use of cyclosporine and corticosteroids. Presently, cases of steroid-resistant CIP remain infrequent, necessitating vigilant and meticulous monitoring within clinical settings. Notably, there exists no distinct guideline specifying a singular agent for rescuing patients unresponsive to corticosteroid therapy. Therefore, cyclosporine emerges as a promising and efficacious treatment alternative for individuals unresponsive to corticosteroid intervention in the context of CIP., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable: Ethical approval for this case report was not requested. All data in this case were derived from the patient’s routine course of treatment with traceability and no experimental interventions or other manipulations beyond standard medical practice were performed. Consent for publication: Written informed consent was obtained from the patient for publication of this case report and accompanying images. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: While immune checkpoint inhibitors (ICIs) are a beacon of hope for non-small cell lung cancer (NSCLC) patients, they can also cause adverse events, including checkpoint inhibitor pneumonitis (CIP). Research shows that the inflammatory immune microenvironment plays a vital role in the development of CIP. However, the role of the immune microenvironment (IME) in CIP is still unclear., Methods: We collected a cohort of NSCLC patients treated with ICIs that included eight individuals with CIP (CIP group) and 29 individuals without CIP (Control group). CIBERSORT and the xCell algorithm were used to evaluate the proportion of immune cells. Gene set enrichment analysis (GSEA) and single-sample GSEA (ssGSEA) were used to evaluate pathway activity. The ridge regression algorithm was used to analyze drug sensitivity., Results: CIBERSORT showed significantly upregulated memory B cells, CD8+ T cells, and M1 Macrophages in the CIP group. The number of memory resting CD4+ T cells and resting NK cells in the CIP group was also significantly lower than in the Control group. The XCell analysis showed a higher proportion of Class-switched memory B-cells and M1 Macrophages in the CIP group. Pathway analysis showed that the CIP group had high activity in their immune and inflammatory response pathways and low activity in their immune exhaustion related pathway., Conclusions: In this study, we researched CIP patients who after ICIs treatment developed an inflammatory IME, which is characterized by significantly increased activated immune cells and expression of inflammatory molecules, as well as downregulated immunosuppressive lymphocytes and signaling pathways. The goal was to develop theoretical guidance for clinical guidelines for the treatment of CIP in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lin, Deng, Deng, Yang, Sun, Zhou, Qin, Xie, Li, Zhong, Song and Zhou.)