Peripheral blood inflammatory score using a cytokine multiplex assay predicts clinical outcomes in patients treated with atezolizumab-bevacizumab for unresectable HCC
BackgroundSeveral 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.MethodsWe examined vari...
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Frontiers Media S.A.
2025-06-01
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| author | Hee Sun Cho Hee Sun Cho Hee Sun Cho Soon Kyu Lee Soon Kyu Lee Ji Won Han Ji Won Han Jung Hyun Kwon Jung Hyun Kwon Soon Woo Nam Soon Woo Nam Jaejun Lee Jaejun Lee Keungmo Yang Keungmo Yang Pil Soo Sung Pil Soo Sung Jeong Won Jang Jeong Won Jang Seung Kew Yoon Seung Kew Yoon Jong Young Choi Jong Young Choi |
| author_facet | Hee Sun Cho Hee Sun Cho Hee Sun Cho Soon Kyu Lee Soon Kyu Lee Ji Won Han Ji Won Han Jung Hyun Kwon Jung Hyun Kwon Soon Woo Nam Soon Woo Nam Jaejun Lee Jaejun Lee Keungmo Yang Keungmo Yang Pil Soo Sung Pil Soo Sung Jeong Won Jang Jeong Won Jang Seung Kew Yoon Seung Kew Yoon Jong Young Choi Jong Young Choi |
| author_sort | Hee Sun Cho |
| collection | DOAJ |
| description | BackgroundSeveral 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.MethodsWe 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.ResultsAmong 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.ConclusionThese 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. |
| format | Article |
| id | doaj-art-db873b848cd141a0b80336c11f34d639 |
| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj-art-db873b848cd141a0b80336c11f34d6392025-08-20T03:46:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-06-011610.3389/fimmu.2025.15784221578422Peripheral blood inflammatory score using a cytokine multiplex assay predicts clinical outcomes in patients treated with atezolizumab-bevacizumab for unresectable HCCHee Sun Cho0Hee Sun Cho1Hee Sun Cho2Soon Kyu Lee3Soon Kyu Lee4Ji Won Han5Ji Won Han6Jung Hyun Kwon7Jung Hyun Kwon8Soon Woo Nam9Soon Woo Nam10Jaejun Lee11Jaejun Lee12Keungmo Yang13Keungmo Yang14Pil Soo Sung15Pil Soo Sung16Jeong Won Jang17Jeong Won Jang18Seung Kew Yoon19Seung Kew Yoon20Jong Young Choi21Jong Young Choi22The Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Internal Medicine, College of Medicine, Eunpyeong St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Internal Medicine, College of Medicine, Incheon St. Mary’s Hospital, The Catholic University of Korea, Incheon, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Internal Medicine, College of Medicine, Incheon St. Mary’s Hospital, The Catholic University of Korea, Incheon, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Internal Medicine, College of Medicine, Incheon St. Mary’s Hospital, The Catholic University of Korea, Incheon, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of KoreaThe Catholic University Liver Research Center, College of Medicine, The Catholic University of Korea, Seoul, Republic of KoreaDepartment of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Republic of KoreaBackgroundSeveral 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.MethodsWe 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.ResultsAmong 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.ConclusionThese 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1578422/fullhepatocellular carcinomaatezolizumab plus bevacizumabprognostic scorebiomarkercytokine |
| spellingShingle | Hee Sun Cho Hee Sun Cho Hee Sun Cho Soon Kyu Lee Soon Kyu Lee Ji Won Han Ji Won Han Jung Hyun Kwon Jung Hyun Kwon Soon Woo Nam Soon Woo Nam Jaejun Lee Jaejun Lee Keungmo Yang Keungmo Yang Pil Soo Sung Pil Soo Sung Jeong Won Jang Jeong Won Jang Seung Kew Yoon Seung Kew Yoon Jong Young Choi Jong Young Choi Peripheral blood inflammatory score using a cytokine multiplex assay predicts clinical outcomes in patients treated with atezolizumab-bevacizumab for unresectable HCC Frontiers in Immunology hepatocellular carcinoma atezolizumab plus bevacizumab prognostic score biomarker cytokine |
| title | Peripheral blood inflammatory score using a cytokine multiplex assay predicts clinical outcomes in patients treated with atezolizumab-bevacizumab for unresectable HCC |
| title_full | Peripheral blood inflammatory score using a cytokine multiplex assay predicts clinical outcomes in patients treated with atezolizumab-bevacizumab for unresectable HCC |
| title_fullStr | Peripheral blood inflammatory score using a cytokine multiplex assay predicts clinical outcomes in patients treated with atezolizumab-bevacizumab for unresectable HCC |
| title_full_unstemmed | Peripheral blood inflammatory score using a cytokine multiplex assay predicts clinical outcomes in patients treated with atezolizumab-bevacizumab for unresectable HCC |
| title_short | Peripheral blood inflammatory score using a cytokine multiplex assay predicts clinical outcomes in patients treated with atezolizumab-bevacizumab for unresectable HCC |
| title_sort | peripheral blood inflammatory score using a cytokine multiplex assay predicts clinical outcomes in patients treated with atezolizumab bevacizumab for unresectable hcc |
| topic | hepatocellular carcinoma atezolizumab plus bevacizumab prognostic score biomarker cytokine |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1578422/full |
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