CASE REPORT article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Immune Checkpoint Inhibitor-Related Encephalitis Overlapping with Hyperprogression in Metastatic Lung Cancer: A Case Report
Provisionally accepted
- Beijing Tiantan Hospital, Capital Medical University, Beijing, China
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Background: Immune checkpoint inhibitors (ICIs) have significantly improved survival in patients with advanced non-small cell lung cancer (NSCLC), but may rarely trigger severe immune-related adverse events (irAEs). Case Summary: A 64-year-oldpatient with metastatic squamous NSCLC and high programmed death-ligand 1 (PD-L1) expression developed subacute neurological decline following pembrolizumab therapy, concurrent with rapid progression. Cerebrospinal fluid (CSF) analysis revealed inflammatory changes featuring markedly elevated IL-6 levels, while serological and imaging studies excluded infection, supporting a diagnosis of ICI-related encephalitis. Despite neurological symptom resolution with corticosteroids and intravenous immunoglobulin, systemic hyperprogressive disease (HPD) emerged, culminating in fatal tumor progression. Conclusion: This case underscores the need for vigilance toward the coexistence of rare neurotoxic irAEs and HPD during ICI therapy. Early recognition, multidisciplinary collaboration, and balanced therapeutic strategies are critical to optimizing outcomes.
Keywords: Encephalitis, Hyperprogressive disease, immune checkpoint inhibitors, Immune-related adverse events, Non-small cell lung cancer
Received: 19 Oct 2025; Accepted: 16 Feb 2026.
Copyright: © 2026 Xu, Cao and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xiaoyan Li
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