Correlation of high serum interleukin-6 with clinical outcome and T cell response in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab.

Authors

Hong Jae Chon

Hongjae Chon

CHA Bundang Medical Center, Seongnam-Si, South Korea;

Hongjae Chon , Chan Kim , Hannah Yang , Jaekyung Cheon , Yeonjung Ha , Sung Hwan Lee , Beodeul Kang , Ilhwan Kim , Hyeyeong Kim , Won Suk Lee , Sanghoon Jung , Vince Gaillard

Organizations

CHA Bundang Medical Center, Seongnam-Si, South Korea; , Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, South Korea; , Department of Medical Oncology, CHA Bundang Medical Center, Seongnam, South Korea; , Division of Oncology, Department of Internal Medicine, Haeundae Paik Hospital, Inje University College of Medicine, Busan, South Korea; , Ulsan Univ Hosp, Univ of Ulsan, Ulsan, South Korea; , Department of Radiology, CHA Bundang Medical Center, Seongnam, South Korea; , Roche, Basel, Switzerland;

Research Funding

Other Government Agency
National Research Foundation of Korea

Background: We elucidated the clinical and immunologic implications of serum interleukin (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 centers; Validation cohort: 81 patients from one center). Baseline blood samples were analyzed using a flow cytometric bead array. The tumor immune microenvironment was analyzed using RNA sequencing. Results: In the Discovery cohort, clinical benefit (CB) was defined as a complete or partial response or stable disease for ≥ 6 months. Among various blood-based biomarkers, the serum IL-6 level was significantly higher in patients without CB than in those with CB (mean 11.56 vs. 5.05 pg/mL, P=0.02). The optimal cutoff value for high IL-6 was determined as 18.49 pg/mL using maximally selected rank statistics, and 15.2% of patients were identified to have high IL-6 levels at baseline. In both the Discovery and Validation cohorts, patients with high baseline IL-6 levels had a reduced response rate and worse progression-free and overall survival after Ate/Bev compared with that of patients with low IL-6 levels. In the multivariable Cox regression analysis, the clinical implication of high IL-6 levels persisted even after adjustment for various confounding factors. Patients with high IL-6 levels showed reduced interferon-γ and tumor necrosis factor-α secretion from CD8+ T cells. Moreover, excess IL-6 suppressed cytokine production and CD8+ T-cell proliferation. Finally, patients with high IL-6 levels exhibited a non-T-cell-inflamed immunosuppressive tumor 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.

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Abstract Details

Meeting

2023 ASCO Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract

Track

Pancreatic Cancer,Hepatobiliary Cancer,Neuroendocrine/Carcinoid,Small Bowel Cancer

Sub Track

Tumor Biology, Biomarkers, and Pathology

Citation

J Clin Oncol 41, 2023 (suppl 4; abstr 596)

DOI

10.1200/JCO.2023.41.4_suppl.596

Abstract #

596

Poster Bd #

F8

Abstract Disclosures