Prospects and Challenges for T Cell-Based Therapies of HCC

Woller, Norman; Engelskircher, Sophie; Wirth, Thomas; Wedemeyer, Heiner

doi:10.3390/cells10071651

Cited by 17 publications

(11 citation statements)

References 148 publications

(175 reference statements)

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“…The relationship between the TME and the cancer cells is very complex (33), and TME is closely related to tumor cell proliferation, apoptosis, and metastasis (34). It has been argued (35) that there are fundamental differences in the composition of immune cells in healthy tissue, adjacent tissue, and cancer tissue. A number of studies (36) have shown that B cells play an antitumor role by directly interacting with tumor cells or assisting other immune functions.…”

Section: Discussionmentioning

confidence: 99%

CCDC25 may be a potential diagnostic and prognostic marker of hepatocellular carcinoma: Results from microarray analysis

et al. 2022

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BackgroundHepatocellular carcinoma (HCC) is a tumor with a high recurrence rate, poor prognosis, and rapid progression. Therefore, it is necessary to find a novel biomarker for HCC. Coiled-coil domain containing 25 (CCDC25) has been identified as a target molecule that mediates liver metastasis in colon cancer. However, the molecular mechanisms of CCDC25 in HCC are unknown. This study aimed to explore the role of CCDC25 in HCC.MethodsThe expression of CCDC25 in HCC was identified through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Receiver operating characteristic curve (ROC) curves were drawn to evaluate the diagnostic value of CCDC25 for HCC. The effect of CCDC25 on the prognosis of HCC was analyzed by using the Kaplan–Meier plotter. Co-expressed genes and Gene Set Enrichment Analysis (GSEA) were used to explore the related functions and regulatory signaling pathways of CCDC25. Moreover, we employed the Tumor Immune Estimation Resource (TIMER) database and CIBERSORT algorithm to investigate the relationship between CCDC25 and the tumor immune microenvironment (TME) in HCC. Meanwhile, the effect of CCDC25 on the sensitivity of HCC patients to chemotherapy drugs was evaluated. Finally, we explored the prognostic methylation sites of CCDC25 using the MethSurv database.ResultsCCDC25 expression was low in HCC. Low CCDC25 expression was significantly associated with poor overall survival of HCC and may be comparable to the ability of AFP to diagnose HCC. Dysregulation of glucose metabolism, fatty acid metabolism, amino acid metabolism, ubiquitination modification, and apoptosis inhibition caused by CCDC25 downregulation may be the causes and results of HCC. In addition, CCDC25 was positively correlated with the infiltration level of various adaptive antitumor immune cells. The levels of immune cell infiltration and immune checkpoint expression were lower in the samples with high CCDC25 expression. What is more, we found that downregulated CCDC25 may increase the sensitivity or resistance of HCC patients to multiple drugs, including sorafenib. We also identified a methylation site for CCDC25, which may be responsible for poor prognosis and low CCDC25 expression in HCC patients. Finally, CCDC25 may be associated with HCC ferroptosis.ConclusionsCCDC25 may be a potential diagnostic and prognostic marker for HCC and is associated with immune infiltration and ferroptosis.

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Section: Discussionmentioning

confidence: 99%

CCDC25 may be a potential diagnostic and prognostic marker of hepatocellular carcinoma: Results from microarray analysis

et al. 2022

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“…Successful immunotherapy relies not only on adequate numbers of TILs but also on the level of immune checkpoint expression [ 30 , 31 ]. For this reason, we examined the link between MELK and immune checkpoints, observing that raised levels of MELK were linked to all the examined checkpoints, implying that targeting MELK could enhance the effectiveness of immunotherapy.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis to identify noncoding RNAs mediated upregulation of maternal embryonic leucine zipper kinase (MELK) correlated with poor prognosis in hepatocellular carcinoma

Guo¹,

Zhu

2022

Aging

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Object: Maternal embryonic leucine zipper kinase (MELK) is involved in the development and progression of various cancers. This work investigated the usefulness of MELK in the prediction of hepatocellular carcinoma (HCC) prognosis. Methods: Information on MELK expression was obtained by pan-cancer analysis using The Cancer Genome Atlas (TCGA) database. The TCGA-liver hepatic cancer (TCGA-LIHC), Oncomine datasets, International Cancer Genome Consortium (ICGC) datasets were used to investigate MELK expression in HCC. The prognostic roles of MELK in HCC were assessed by univariate and multivariate survival analyses. The underlying mechanism for noncoding RNAs (ncRNAs) involved in MELK expression was investigated by in silico studies, correlation, methylation, and survival analyses. The relationships between MELK expression and immune cells, immune markers, and checkpoint markers were also analyzed. Results: (1) MELK was identified as an independent predictor of overall survival (OS) in HCC patients (MELK high vs. low expression, HR 2.469; 95% CI 1.217–5.008; p = 0.012) in a multivariate Cox analysis, with a concordance index (C-index) value of 0.727 (95% CI 0.750–0.704). (2) The noncoding RNA miR3142HG and the LINC00265/has-miR-101-3p axis were found to regulate MELK expression in HCC tissue. (3) MELK levels were linked to various immune functions, including tumor infiltration and the expression of immune checkpoints and biomarkers in HCC. Conclusion: MELK may have an oncogenic function in HCC and was found to be up-regulated by ncRNAs and associated with immune cell infiltration and unfavorable prognosis.

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“…Oncolytic viruses, cancer vaccines ( 96 ), pericyte therapy ( 97 ), photothermal therapy (PTT) and photodynamic therapy (PDT) ( 98 ), and nanotechnology are also being explored. However, due to the specific immune tolerance of the liver ( 99 ) and the complexity of the tumor microenvironment, the treatment of hepatocellular carcinoma remains a great challenge, and continuous research, including single-cell sequencing, is needed in the future to explore new immunotherapeutic targets and personalized treatment protocols ( 100 ). In addition to this, the development of diagnostic, prognostic and biomarker prediction for hepatocellular carcinoma and other cancers using artificial intelligence is an exciting prospect ( 101 ).…”

Section: Discussionmentioning

confidence: 99%

Feasibility of hepatocellular carcinoma treatment based on the tumor microenvironment

et al. 2022

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The incidence of liver cancer is extremely high worldwide and poses a serious threat to human life and health. But at present, apart from radiotherapy, chemotherapy, liver transplantation, and early resection, sorafenib was the main systemic therapy proven to have clinical efficacy for unresectable liver cancer (HCC) until 2017. Despite the emerging immunotherapy in the past decade with immune inhibitors such as PD - 1 being approved and applied to clinical treatment, there are still some patients with no response. This review aims to elucidate the mechanisms underlying the tumor microenvironment of hepatocellular carcinoma and thus analyze the effectiveness of targeting the tumor microenvironment to improve the therapeutic efficacy of hepatocellular carcinoma, including the effectiveness and feasibility of immunotherapy, tumor oncolytic viruses and anti-vascular proliferation therapy.

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Prospects and Challenges for T Cell-Based Therapies of HCC

Cited by 17 publications

References 148 publications

CCDC25 may be a potential diagnostic and prognostic marker of hepatocellular carcinoma: Results from microarray analysis

CCDC25 may be a potential diagnostic and prognostic marker of hepatocellular carcinoma: Results from microarray analysis

Comprehensive analysis to identify noncoding RNAs mediated upregulation of maternal embryonic leucine zipper kinase (MELK) correlated with poor prognosis in hepatocellular carcinoma

Feasibility of hepatocellular carcinoma treatment based on the tumor microenvironment

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