ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1578422
This article is part of the Research TopicCommunity Series in Biomarkers in the Era of Cancer Immunotherapy: Zooming in from Periphery to Tumor Microenvironment, Volume IIIView all 4 articles
Peripheral Blood Inflammatory Score Using a Cytokine Multiplex Assay Predicts Clinical Outcomes in Patients Treated with Atezolizumab-Bevacizumab for Unresectable HCC
Provisionally accepted
Hee Sun Cho1,2,3
Soon Kyu Lee1,3,4
Ji Won Han1,3,5*
Jung Hyun Kwon1,3,4Soon Woo Nam1,3,4
Jaejun Lee1,3,5Keungmo Yang1,3,5
Pil Soo Sung1,3,5
Jeong Won Jang1,3,5
Seung Kew Yoon1,3,5
Jong Young Choi1,3,5- 1Catholic University of Korea, Seoul, Republic of Korea
- 2Eunpyeong St. Mary's Hospital, Catholic University of Korea, Seoul, Republic of Korea
- 3The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea
- 4Incheon St. Mary's Hospital, Incheon, Republic of Korea
- 5Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Seoul, Republic of Korea
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Background: Several serum cytokines have been proposed as biomarkers for predicting the outcomes of patients with hepatocellular carcinoma (HCC) receiving tyrosine kinase inhibitors. However, their role in atezolizumab plus bevacizumab (AB) treatment needs to be more elucidated.We examined various serum cytokines, including interferon-γ (IFN-γ), interleukin-10 (IL-10), IL-12, IL-17, IL-2, IL-6, and tumor necrosis factor, using a Luminex cytokine multiplex assay before AB treatment in prospectively enrolled 116 AB-treatment patients for the derivation cohort and 54 patients for the external validation cohort. We collected baseline characteristics, including neutrophil-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels, and prospectively observed clinical outcomes.Results: Among various peripheral blood inflammatory markers, high NLR, CRP, IL-2, and IL-12 levels were significantly associated with poor progression-free survival (PFS) and overall survival (OS) in patients with AB-treated HCC. Through sensitivity analysis, we defined the high peripheral blood inflammatory score (PBIS) group, which included two or more of the following elevated factors: NLR, CRP, IL-2, and IL-12. The high PBIS group had elevated serum inflammatory cytokines and a higher tumor burden than the low PBIS group.A high PBIS score was an independent risk factor associated with poor OS, PFS, and objective response rate (ORR) in multivariate analyses, which was also confirmed in the validation cohort and propensity score-matched cohort. However, it was not a significant factor for OS, PFS, or ORR in lenvatinib-treated patients.These results suggest that a peripheral blood marker-based scoring system can significantly predict clinical outcomes in patients with AB-treated HCC. This non-invasive biomarker is expected to be a potential predictive and prognostic factor for AB treatment.
Keywords: hepatocellular carcinoma, atezolizumab plus bevacizumab, cytokine, prognostic score, biomarker HCC, hepatocellular carcinoma, AB, atezolizumab plus bevacizumab, IL, Interleukin, NLR, Neutrophil-lymphocyte ratio, CRP, C-reactive protein, PFS, progressionfree survival, OS, overall survival, ORR, objective response rate
Received: 17 Feb 2025; Accepted: 26 May 2025.
Copyright: © 2025 Cho, Lee, Han, Kwon, Nam, Lee, Yang, Sung, Jang, Yoon and Choi. 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: Ji Won Han, Catholic University of Korea, Seoul, Republic of Korea
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