The vessels encapsulating tumor clusters (VETC) pattern is a negative predictor for first-line immune checkpoint inhibitors alone in unresectable hepatocellular carcinoma.
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Hepatocellular Carcinoma Treatment and Prognosis
Cancer Immunotherapy and Biomarkers
Ferroptosis and cancer prognosis
[BACKGROUND] Vessels encapsulating tumor clusters (VETC), an aggressive pathological pattern in hepatocellular carcinoma (HCC), is associated with unfavorable clinical outcomes.
- 표본수 (n) 34
- p-value P = 0.003
- p-value P = 0.005
- HR 3.42
- 추적기간 47.9 months
APA
Chun-Yu Lin, Shuai Kang, et al. (2026). The vessels encapsulating tumor clusters (VETC) pattern is a negative predictor for first-line immune checkpoint inhibitors alone in unresectable hepatocellular carcinoma.. Journal of gastroenterology. https://doi.org/10.1007/s00535-026-02421-5
MLA
Chun-Yu Lin, et al.. "The vessels encapsulating tumor clusters (VETC) pattern is a negative predictor for first-line immune checkpoint inhibitors alone in unresectable hepatocellular carcinoma.." Journal of gastroenterology, 2026.
PMID
42029729
Abstract
[BACKGROUND] Vessels encapsulating tumor clusters (VETC), an aggressive pathological pattern in hepatocellular carcinoma (HCC), is associated with unfavorable clinical outcomes. However, its role in first-line systemic therapies-immune checkpoint inhibitors alone (ICI-alone), tyrosine kinase inhibitors (TKIs) alone, or ICIs-based combinations (ICI-combo)-remains largely unexplored. This study aimed to compare therapy efficacy in unresectable HCC (uHCC) stratified by VETC.
[METHODS] A retrospective analysis of 111 uHCC patients (ICI-alone, n = 34; TKIs, n = 24; ICI-combo, n = 53) used pooled data from 19 prospective studies (2017-2024). Objective response rate (ORR), investigator-assessed progression-free survival (PFS), overall survival (OS), and pathological characteristics were investigated. Tumor immune microenvironment was compared between the VETC and non-VETC by immunohistochemistry and transcriptome sequencing.
[RESULTS] With a median follow-up of 47.9 months, ICI-combo cohort demonstrated significantly superior ORR (49.1% vs. 20.6% [ICI-alone] vs. 16.7% [TKIs], P = 0.003) and mPFS (8.57 vs. 2.10 vs. 3.97 months, P = 0.005), though no significant difference in OS was observed (median, 19.27 vs. 12.87 vs. 13.90 months, P = 0.070). VETC-positive patients receiving ICI-alone had markedly inferior outcomes (DCR, 9.1%; mPFS, 1.63 months; mOS, 3.47 months) compared to those receiving TKIs or ICI-combo (P < 0.05). Multivariate analysis confirmed VETC as an independent negative OS predictor in the ICI-alone cohort (HR = 3.42, P = 0.013). VETC tumors exhibited an immunosuppressive microenvironment (reduced CD8 T/CD20 B-cell infiltration and M2-like macrophage dominance), corroborated by transcriptomic downregulation of T/B cells and M1 macrophage-related genes.
[CONCLUSIONS] VETC, characterized by reduced immune infiltration, is a negative predictor of first-line ICIs alone in uHCC, guiding personalized treatment selection in uHCC.
[METHODS] A retrospective analysis of 111 uHCC patients (ICI-alone, n = 34; TKIs, n = 24; ICI-combo, n = 53) used pooled data from 19 prospective studies (2017-2024). Objective response rate (ORR), investigator-assessed progression-free survival (PFS), overall survival (OS), and pathological characteristics were investigated. Tumor immune microenvironment was compared between the VETC and non-VETC by immunohistochemistry and transcriptome sequencing.
[RESULTS] With a median follow-up of 47.9 months, ICI-combo cohort demonstrated significantly superior ORR (49.1% vs. 20.6% [ICI-alone] vs. 16.7% [TKIs], P = 0.003) and mPFS (8.57 vs. 2.10 vs. 3.97 months, P = 0.005), though no significant difference in OS was observed (median, 19.27 vs. 12.87 vs. 13.90 months, P = 0.070). VETC-positive patients receiving ICI-alone had markedly inferior outcomes (DCR, 9.1%; mPFS, 1.63 months; mOS, 3.47 months) compared to those receiving TKIs or ICI-combo (P < 0.05). Multivariate analysis confirmed VETC as an independent negative OS predictor in the ICI-alone cohort (HR = 3.42, P = 0.013). VETC tumors exhibited an immunosuppressive microenvironment (reduced CD8 T/CD20 B-cell infiltration and M2-like macrophage dominance), corroborated by transcriptomic downregulation of T/B cells and M1 macrophage-related genes.
[CONCLUSIONS] VETC, characterized by reduced immune infiltration, is a negative predictor of first-line ICIs alone in uHCC, guiding personalized treatment selection in uHCC.
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