ArticleGastroenterology report2025
In-depth plasma proteomics reveals the dynamic changes and prognostic biomarkers for chimeric antigen receptor-glypican-3 T-cell therapy in patients with hepatocellular carcinoma.
Article in Gastroenterology report, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Chimeric antigen receptor (CAR) T-cell therapy has shown notable advancements in the treatment of solid tumors. Nevertheless, its effectiveness is limited to a small group of patients, highlighting the need for predictive biomarkers. This study aimed to investigate biomarkers associated with the efficacy of CAR-T therapy in hepatocellular carcinoma (HCC). Methods: We prospectively collected plasma samples from 17 patients with HCC before and after they underwent CAR-glypican-3 (GPC3) T-cell therapy as part of three clinical trials. Plasma proteomic profiling was conducted by using liquid chromatography-mass spectrometry. We examined sequential plasma samples to evaluate the impact of CAR T-cell therapy on the systemic plasma proteome. Additionally, we compared the pretreatment plasma protein profiles between groups with and without clinical benefit (CB) to identify proteins linked to treatment efficacy. The Cox proportional hazard model was used to evaluate the relationship between plasma protein levels and survival outcomes. Results: Among 5337 plasma proteins, 225 exhibited significant changes following CAR-GPC3 T-cell therapy. The CB group showed an increased expression in proteins related to the type I interferon signaling pathway, T-cell proliferation and activation, tumor necrosis factor production, and antigen processing and presentation. In addition, plasma proteins were significantly associated with survival outcomes, whereas no significant association was observed between clinical variables and prognosis. Conclusions: Plasma proteomics not only captured CAR-GPC3-driven plasma microenvironment remodeling but also identified baseline proteins predictive of CB and survival, which were superior to clinical variables, thus constituting a candidate biomarker panel for HCC patient selection and response monitoring.
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