Cited 16 times in
High serum IL-6 correlates with reduced clinical benefit of atezolizumab and bevacizumab in unresectable hepatocellular carcinoma
DC Field | Value | Language |
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dc.contributor.author | 라선영 | - |
dc.contributor.author | 강버들 | - |
dc.date.accessioned | 2024-02-15T06:58:30Z | - |
dc.date.available | 2024-02-15T06:58:30Z | - |
dc.date.issued | 2023-04 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/198097 | - |
dc.description.abstract | Background & Aims: We elucidated the clinical and immunologic implications of serum IL-6 levels in patients with unresectable hepatocellular carcinoma (HCC) treated with atezolizumab and bevacizumab (Ate/Bev). Methods: We prospectively enrolled 165 patients with unresectable HCC (discovery cohort: 84 patients from three centres; validation cohort: 81 patients from one centre). Baseline blood samples were analysed using a flow cytometric bead array. The tumour immune microenvironment was analysed using RNA sequencing. Results: In the discovery cohort, clinical benefit 6 months (CB6m) was defined as complete or partial response, or stable disease for ≥6 months. Among various blood-based biomarkers, serum IL-6 levels were significantly higher in participants without CB6m than in those with CB6m (mean 11.56 vs. 5.05 pg/ml, p = 0.02). Using maximally selected rank statistics, the optimal cut-off value for high IL-6 was determined as 18.49 pg/ml, and 15.2% of participants were found to have high IL-6 levels at baseline. In both the discovery and validation cohorts, participants with high baseline IL-6 levels had a reduced response rate and worse progression-free and overall survival after Ate/Bev treatment compared with those with low baseline IL-6 levels. In multivariable Cox regression analysis, the clinical implications of high IL-6 levels persisted, even after adjusting for various confounding factors. Participants with high IL-6 levels showed reduced interferon-γ and tumour necrosis factor-α secretion from CD8+ T cells. Moreover, excess IL-6 suppressed cytokine production and proliferation of CD8+ T cells. Finally, participants with high IL-6 levels exhibited a non-T-cell-inflamed immunosuppressive tumour microenvironment. Conclusions: High baseline IL-6 levels can be associated with poor clinical outcomes and impaired T-cell function in patients with unresectable HCC after Ate/Bev treatment. Impact and implications: Although patients with hepatocellular carcinoma who respond to treatment with atezolizumab and bevacizumab exhibit favourable clinical outcomes, a fraction of these still experience primary resistance. We found that high baseline serum levels of IL-6 correlate with poor clinical outcomes and impaired T-cell response in patients with hepatocellular carcinoma treated with atezolizumab and bevacizumab. © 2023 The Author(s) | - |
dc.description.statementOfResponsibility | open | - |
dc.format | application/pdf | - |
dc.language | English | - |
dc.publisher | Elsevier B.V. | - |
dc.relation.isPartOf | JHEP REPORTS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.title | High serum IL-6 correlates with reduced clinical benefit of atezolizumab and bevacizumab in unresectable hepatocellular carcinoma | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Hannah Yang | - |
dc.contributor.googleauthor | Beodeul Kang | - |
dc.contributor.googleauthor | Yeonjung Ha | - |
dc.contributor.googleauthor | Sung Hwan Lee | - |
dc.contributor.googleauthor | Ilhwan Kim | - |
dc.contributor.googleauthor | Hyeyeong Kim | - |
dc.contributor.googleauthor | Won Suk Lee | - |
dc.contributor.googleauthor | Gwangil Kim | - |
dc.contributor.googleauthor | Sanghoon Jung | - |
dc.contributor.googleauthor | Sun Young Rha | - |
dc.contributor.googleauthor | Vincent E Gaillard | - |
dc.contributor.googleauthor | Jaekyung Cheon | - |
dc.contributor.googleauthor | Chan Kim | - |
dc.contributor.googleauthor | Hong Jae Cho | - |
dc.identifier.doi | 10.1016/j.jhepr.2023.100672 | - |
dc.contributor.localId | A01316 | - |
dc.relation.journalcode | J04267 | - |
dc.identifier.eissn | 2589-5559 | - |
dc.identifier.pmid | 36866388 | - |
dc.subject.keyword | AFP, alpha-foetoprotein | - |
dc.subject.keyword | Ate/Bev, atezolizumab and bevacizumab | - |
dc.subject.keyword | Atezolizumab | - |
dc.subject.keyword | BCLC, Barcelona Clinic Liver Cancer | - |
dc.subject.keyword | Bevacizumab | - |
dc.subject.keyword | CB6m, clinical benefit 6 months | - |
dc.subject.keyword | CONSORT, Consolidated Standards of Reporting Trials | - |
dc.subject.keyword | CR, complete response | - |
dc.subject.keyword | CRAFITY, C-reactive protein and AFP in immunotherapy | - |
dc.subject.keyword | CTLA-4, cytotoxic T-lymphocyte-associated protein 4 | - |
dc.subject.keyword | DC, dendritic cell | - |
dc.subject.keyword | ECOG, Eastern Cooperative Oncology Group | - |
dc.subject.keyword | FFPE, formalin-fixed paraffin-embedded | - |
dc.subject.keyword | HCC, hepatocellular carcinoma | - |
dc.subject.keyword | HR, hazard ratio | - |
dc.subject.keyword | Hepatocellular carcinoma | - |
dc.subject.keyword | IFN-γ, interferon-γ | - |
dc.subject.keyword | IL-6 | - |
dc.subject.keyword | Immunotherapy | - |
dc.subject.keyword | MDSC, myeloid-derived suppressor cell | - |
dc.subject.keyword | MSI, microsatellite instability | - |
dc.subject.keyword | MVI, macrovascular invasion | - |
dc.subject.keyword | ORR, objective response rate | - |
dc.subject.keyword | OS, overall survival | - |
dc.subject.keyword | PBMC, peripheral blood mononuclear cell | - |
dc.subject.keyword | PD, progressive disease | - |
dc.subject.keyword | PD-1, programmed-death-1 | - |
dc.subject.keyword | PD-L1, programmed-death ligand-1 | - |
dc.subject.keyword | PFS, progression-free survival | - |
dc.subject.keyword | PR, partial response | - |
dc.subject.keyword | RECIST, Response Evaluation Criteria in Solid Tumours | - |
dc.subject.keyword | SD, stable disease | - |
dc.subject.keyword | TME, tumour microenvironment | - |
dc.subject.keyword | TNF-α, tumour necrosis factor-α | - |
dc.subject.keyword | VEGF, vascular endothelial growth factor | - |
dc.contributor.alternativeName | Rha, Sun Young | - |
dc.contributor.affiliatedAuthor | 라선영 | - |
dc.citation.volume | 5 | - |
dc.citation.number | 4 | - |
dc.citation.startPage | 100672 | - |
dc.identifier.bibliographicCitation | JHEP REPORTS, Vol.5(4) : 100672, 2023-04 | - |
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