ArticleFrontiers in immunology2022
Hepatic Tumor Stiffness Measured by Shear Wave Elastography Is Prognostic for HCC Progression Following Treatment With Anti-PD-1 Antibodies Plus Lenvatinib: A Retrospective Analysis of Two Independent Cohorts.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 14 citations in OpenAlex.
- The mechano-immunological barrier in fibrosis-associated lung cancer: targeting matrix stiffness and the Piezo1 axis for microenvironment normalization.Frontiers in pharmacology · 2026Review
- Extracellular matrix stiffness in hepatocellular carcinoma: mechanisms and targeted therapeutic strategies.Frontiers in immunology · 2026Review
- Mechanical Microenvironment in Tumor Immune Evasion: Bidirectional Regulation Between Matrix Stiffness and Immune Cells and Its Therapeutic Implications.International journal of biological sciences · 2026Review
- Lenvatinib and immune-checkpoint inhibitors in hepatocellular carcinoma: mechanistic insights, clinical efficacy, and future perspectives.Journal of hematology & oncology · 2024Review
- Tumor-ColonizingBiomolecules · 2024Article
- Modulating extracellular matrix stiffness: a strategic approach to boost cancer immunotherapy.Cell death & disease · 2024Review
- Enhancing HCC Treatment: innovatively combining HDAC2 inhibitor with PD-1/PD-L1 inhibition.Cancer cell international · 2023Review
- CAXII inhibitors: Potential sensitizers for immune checkpoint inhibitors in HCC treatment.Frontiers in immunology · 2023Review
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: The clinical significance of liver stiffness (LS) measured by shear wave elastography (SWE) in programmed cell death protein-1 (PD-1) inhibitors treated advanced hepatocellular carcinoma (HCC) patients remains unknown. This study aimed to explore the prognostic value of baseline LS by SWE prior to PD-1 inhibitor treatment in combination with lenvatinib. Methods: We retrospectively evaluated patients (n=133) with HCC who received anti-PD-1 antibodies plus lenvatinib at two high-volume medical centres, between January 2020 and June 2021. Univariate and multivariate logistic regression analysis were used to develop a novel nomogram. RNA sequencing and immunohistochemical staining were used to assess the heterogeneity of biological and immune characteristics associated with tumor stiffness. Results: The objective response rate (ORR) and disease control rate (DCR) of the whole population were 23.4% and 72.2%, respectively. A LS value of the baseline tumorous foci of 19.53 kPa had the maximum sum of sensitivity and specificity, making it the optimal cut-off value for predicting PD-1 inhibitor efficacy. The nomogram comprised baseline tumor LS and albumin-bilirubin grade (ALBI), which provided favorable calibration and discrimination in the training dataset with an AUC of 0.840 (95%CI: 0.750-0.931) and a C-index of 0.828. Further, it showed acceptable discrimination in the validation cohort, with an AUC of 0.827 (95%CI: 0.673-0.980) and C-index of 0.803. The differentially expressed genes enriched in high stiffness tumors were predominantly associated with metabolic pathways, while those enriched in low stiffness tumors were related to DNA damage repair. Furthermore, patients with high stiffness tumors had a relatively lower infiltration of immune cells and histone deacetylase pathway inhibitors were identified as candidate drugs to promote the efficacy of immunotherapy. Conclusions: Baseline LS value of tumorous foci by SWE-that is, before administration of a PD-1 inhibitor in combination with lenvatinib-is a convenient predictor of PD-1 inhibitor efficacy in patients with advanced HCC, which has potential to be used for pretreatment stratification to optimize treatment of advanced HCC.
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