ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicThe Role of Immunotherapy in Cancer Therapy and Its ChallengesView all 11 articles
Immune checkpoint inhibitor therapy in advanced cancer: clinical association of irAEs type, inflammatory markers and efficacy
Provisionally accepted
- 1School of Pharmacy, Shandong Second Medical University, Weifang, China
- 2Department of Clinical Pharmacy, The 960th Hospital of the Chinese People's Liberation Army Joint Logistics Support Force, Jinan, China
- 3School of Pharmacy, Jinzhou Medical University, Jinzhou, China
- 4Jinan Key Laboratory of Individualised Clinical Drug Safety Monitoring and Pharmacovigilance Research, Jinan, China
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BACKGROUND: Immune checkpoint inhibitors (ICIs) improve survival in advanced cancers but are associated with immune-related adverse events (irAEs), whose prognostic impact remains debated. The role of systemic inflammatory biomarkers is also not fully defined. METHODS: This research merged a comprehensive systematic review and meta-analysis of 38 studies involving 55,966 participants with a multicenter retrospective cohort study of 870 patients receiving ICI therapy. The aim of this study was to examine the association between irAE characteristics and severity, and baseline inflammatory indicators (NLR, dNLR and PLR), with clinical outcomes, particularly survival (OS) and disease progression survival (PFS). The data were analyzed through time-dependent cox model and meta-analysis. RESULTS: Among 870 immunotherapy patients, 32.4% developed irAEs, predominantly grade 1-2 (83.9%). Severe irAEs (grade >2) significantly increased mortality (OS HR=1.93). Organ-specific analysis identified endocrine (HR=0.938, p < 0.001) and skin toxicity (HR=0.763, p<0.001) as independent protective factors for OS, while hepatic (HR=1.602, p=0.031) and cardiac toxicity (HR=1.181, p=0.017) were risk factors. Elevated baseline inflammatory 2 markers—MLR >0.47 (HR=3.37), NLR >3.45 (HR=2.24), and PLR >186.98 (HR=2.10)—also predicted poorer OS. A meta-analysis confirmed that low-grade irAEs (grade ≤2) conferred significant survival benefit (OS HR=0.54), particularly skin and endocrine toxicities. These findings support irAEs as biomarkers of immunotherapy response, with prognostic relevance shaped by severity and organ involvement. CONCLUSIONS: The prognosis of irAEs depends on organ involvement and severity. Endocrine and skin toxicities confer survival benefits, while severe, hepatic, and cardiac events pose significant risks. Inflammatory markers predict survival but not irAE onset.
Keywords: immune checkpoint inhibitors, Inflammatory biomarkers, Immune-related adverse events, overall survival, Meta-analysis
Received: 09 Jul 2025; Accepted: 12 Nov 2025.
Copyright: © 2025 Qian, Ma, Zhao, Lin, Duan and Guo. 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: Jin-min Guo, gjm90h@126.com
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