Development and Validation of TACE Refractoriness-Related Diagnostic and Prognostic Scores and Characterization of Tumor Microenvironment Infiltration in Hepatocellular Carcinoma

He, Qifan; Yang, Jian; Jin, Yonghai

doi:10.3389/fimmu.2022.869993

Cited by 20 publications

(17 citation statements)

References 66 publications

(67 reference statements)

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“…VEGF was also reported to modulate the checkpoint expression of CD8+T cells in HCC ( 72 ). The expression of PD-1 increased in peripheral mononuclear cells ( 6 , 7 ). ICIs activate interferon-γ (IFN-γ)+ Type 1 T helper (Th1) cells to normalize the tumor vasculars and improve hypoxic environments ( 6 ).…”

Section: Why the Combination Therapy Of Lenvatinib Plus Tace With Pd-...mentioning

confidence: 99%

“…However, repeated TACE treatment could decrease the liver function and cause failure to accept follow-up systematic treatment. The increased times of TACE treatment resulted in the decline in the response rate of tumor tissue to treatment (6)(7)(8)(9). The phenomenon was known as TACE refractoriness/TACE failure, which was defined by the Japan Society of Hepatology in 2010 (7).…”

Section: Introductionmentioning

confidence: 99%

“…The increased times of TACE treatment resulted in the decline in the response rate of tumor tissue to treatment (6)(7)(8)(9). The phenomenon was known as TACE refractoriness/TACE failure, which was defined by the Japan Society of Hepatology in 2010 (7). What occurs if systemic therapy is applied before TACE treatment?…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Lenvatinib plus transarterial chemoembolization with or without immune checkpoint inhibitors for unresectable hepatocellular carcinoma: A review

Sun

Xu²,

Meng

et al. 2022

Front. Oncol.

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Lenvatinib plus transarterial chemoembolization (TACE)have become the first choice for patients with hepatocellular carcinoma (HCC) that are unsuitable for TACE. Sorafenib plus TACE therapy for patients with portal vein tumor thrombus (PVTT) achieved positive results. However, Lenvatinib plus TACE appeared to achieve a more advantageous result for these patients based on the phase 3 REFLECT trial. Both TACE and lenvatinib therapy have immune-stimulating effects, so would lenvatinib plus TACE and immune checkpoint inhibitors be an advantageous therapy for unresectable HCC (uHCC)? Thirteen articles from PubMed were explored to determine the efficacy and safety of lenvatinib plus TACE with or without PD-1 inhibitors therapy. Most of the adverse events (AEs) were manageable. Lenvatinib plus TACE therapy was superior to lenvatinib monotherapy with intermediate stage HCC especially beyond up-to-seven criterion and was superior to TACE monotherapy in patients with uHCC or sorafenib plus TACE therapy in patients with PVTT. Objective response rates (ORRs) of 53.1%–75%, median progression free survival (PFS) of 6.15–11.6 months, and median overall survival (OS) of 14.5–18.97 months were achieved in the lenvatinib plus TACE group. Levatinib plus TACE and PD-1 inhibitors achieved ORRs of 46.7% –80.6%, median PFS of 7.3–13.3 months, and median OS of 16.9–24 months. Control studies also confirmed the triple therapy was superior to lenvatinib plus TACE in patients with uHCC. Overall, the triple therapy is a promising treatment for patients with uHCC, including main PVTT and extrahepatic metastasis. Lenvatinib plus TACE therapy was also preferable for intermediate stage HCC beyond up-to-seven criterion and for patients with PVTT.

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Section: Why the Combination Therapy Of Lenvatinib Plus Tace With Pd-...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Lenvatinib plus transarterial chemoembolization with or without immune checkpoint inhibitors for unresectable hepatocellular carcinoma: A review

Sun

Xu²,

Meng

et al. 2022

Front. Oncol.

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“…We assessed the top 30 mutated genes in both risk groups. Furthermore, we determined several checkpoint genes (CD274, CTLA4, HAVCR2, LAG3, PDCD1, and TIGIT) and found that most checkpoint genes had higher expression in the high-risk group ( 31 ). The oncoplot of TMB and expression levels of checkpoint genes were shown in Figure 7 .…”

Section: Resultsmentioning

confidence: 99%

Identification of a CD4+ conventional T cells-related lncRNAs signature associated with hepatocellular carcinoma prognosis, therapy, and tumor microenvironment

Zhu

Zhang

et al. 2023

Front. Immunol.

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BackgroundHepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, and CD4+ T lymphocytes can inhibit hepatocarcinogenesis and mediate tumor regression. However, few studies have focused on the prognostic power of CD4+ Tconv-related lncRNAs in HCC patients.MethodWe obtained data from TCGA and GEO databases and identified CD4+Tconv-related lncRNAs in HCC. The risk score was constructed using lasso regression and the model was validated using two validation cohorts. The RS was also assessed in different clinical subgroups, and a nomogram was established to further predict the patients’ outcomes. Furthermore, we estimated the immune cell infiltration and cancer-associated fibroblasts (CAFs) through TIMER databases and assessed the role of RS in immune checkpoint inhibitors response.ResultsWe constructed a CD4+ Tconv-related lncRNAs risk score, including six lncRNAs (AC012073.1, AL031985.3, LINC01060, MKLN1-AS, MSC-AS1, and TMCC1-AS1), and the RS had good predictive ability in validation cohorts and most clinical subgroups. The RS and the T stage were included in the nomogram with optimum prediction and the model had comparable OS prediction power compared to the AJCC. Patients in the high-risk group had a poor immune response phenotype, with high infiltrations of macrophages, CAFs, and low infiltrations of NK cells. Immunotherapy and chemotherapy response analysis indicated that low-risk group patients had good reactions to immune checkpoint inhibitors.ConclusionWe constructed and validated a novel CD4+ Tconv-related lncRNAs RS, with the potential predictive value of HCC patients’ survival and immunotherapy response.

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“…Finally, 365 tumor samples from the TCGA-LIHC cohort and 221 tumor samples from the GSE14520 cohort were included. Moreover, to study TACE response, we obtained gene expression profile data from GSE104580, which included 100 TACE-responsive samples and 100 TACE-refractory samples ( He et al, 2022 ). Both somatic mutation data and CNV data were obtained from the TCGA-LIHC cohort, including 371 tumor samples.…”

Section: Methodsmentioning

confidence: 99%

The role of hypoxia-related genes in TACE-refractory hepatocellular carcinoma: Exploration of prognosis, immunological characteristics and drug resistance based on onco-multi-OMICS approach

Cheng

Li²,

Lin³

et al. 2022

Front. Pharmacol.

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Transcatheter arterial chemoembolization (TACE) is an effective treatment for hepatocellular carcinoma (HCC). During TACE, chemotherapeutic agents are locally infused into the tumor and simultaneously cause hypoxia in tumor cells. Importantly, the poor effect of TACE in some HCC patients has been shown to be related to dysregulated expression of hypoxia-related genes (HRGs). Therefore, we identified 33 HRGs associated with TACE (HRGTs) by differential analysis and characterized the mutational landscape of HRGTs. Among 586 HCC patients, two molecular subtypes reflecting survival status were identified by consistent clustering analysis based on 24 prognosis-associated HRGs. Comparing the transcriptomic difference of the above molecular subtypes, three molecular subtypes that could reflect changes in the immune microenvironment were then identified. Ultimately, four HRGTs (CTSO, MMP1, SPP1, TPX2) were identified based on machine learning approachs. Importantly, risk assessment can be performed for each patient by these genes. Based on the parameters of the risk model, we determined that high-risk patients have a more active immune microenvironment, indicating “hot tumor” status. And the Tumor Immune Dysfunction and Exclusion (TIDE), the Cancer Immunome Atlas (TCIA), and Genome of Drug Sensitivity in Cancer (GDSC) databases further demonstrated that high-risk patients have a positive response to immunotherapy and have lower IC50 values for drugs targeting cell cycle, PI3K/mTOR, WNT, and RTK related signaling pathways. Finally, single-cell level analysis revealed significant overexpression of CTSO, MMP1, SPP1, and TPX2 in malignant cell after PD-L1/CTLA-4 treatment. In conclusion, Onco-Multi-OMICS analysis showed that HRGs are potential biomarkers for patients with refractory TACE, and it provides a novel immunological perspective for developing personalized therapies.

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Development and Validation of TACE Refractoriness-Related Diagnostic and Prognostic Scores and Characterization of Tumor Microenvironment Infiltration in Hepatocellular Carcinoma

Cited by 20 publications

References 66 publications

Lenvatinib plus transarterial chemoembolization with or without immune checkpoint inhibitors for unresectable hepatocellular carcinoma: A review

Lenvatinib plus transarterial chemoembolization with or without immune checkpoint inhibitors for unresectable hepatocellular carcinoma: A review

Identification of a CD4+ conventional T cells-related lncRNAs signature associated with hepatocellular carcinoma prognosis, therapy, and tumor microenvironment

The role of hypoxia-related genes in TACE-refractory hepatocellular carcinoma: Exploration of prognosis, immunological characteristics and drug resistance based on onco-multi-OMICS approach

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