Transforming primary human hepatocytes into hepatocellular carcinoma with genetically defined factors

Jiang, Zhiwu; Cheng, Lin; Wu, Zhiping; Zhou, Linfu; Wang, Haitao; Hong, Qilan; Wu, Qianni; Long, Youguo; Huang, Yunlin; Xu, Gaoqi; Yao, Yao; Tang, Zhaoyang; Zhang, Zhenfeng; Yang, Lili; Luo, Wei; Yang, Jie; Gong, Likun; Chen, Xinwen; Cui, Shuzhong; Zhang, Qi; Li, Yin-xiong; Li, Peng

doi:10.15252/embr.202154275

Cited by 10 publications

(8 citation statements)

References 76 publications

(90 reference statements)

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“…It has been reported that FAP was expressed in the stroma of human colorectal tumors and other epithelial malignancies, and it was almost undetected in most normal tissues (Garin‐Chesa et al, 1990). It has been reported that FAP was expressed in induced HCC but not in normal livers (Jiang et al, 2022), and FAP was highly expressed in advance‐staged HCC tumors compared to early lesions (Zou et al, 2018). The colon tumors patients with high FAP expression were correlated with a high risk of metastasis and recurrence (Henry et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that FAP was expressed in induced HCC but not in normal livers (Jiang et al, 2022), and FAP was highly expressed in advance-staged HCC tumors compared to early lesions ( Zou et al, 2018). The colon tumors patients with high FAP expression were correlated with a high risk of metastasis and recurrence (Henry et al, 2007).…”

Section: Fap Overexpression In Cafs Promoted Proliferation and Migrat...mentioning

confidence: 99%

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Fibroblast activation protein promotes progression of hepatocellular carcinoma via regulating the immunity

Wang,

Niu,

Yang

et al. 2024

Cell Biology International

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Fibroblast activation protein (FAP) has been indicated to express in cancer‐associated fibroblasts (CAFs) in most cancers. This work was dedicated to exploring FAP's effects on hepatocellular carcinoma (HCC). The data were extracted from The Cancer Genome Atlas, Gene Expression Omnibus, ImmPort, and Reactome databases. The correlation between FAP and HCC patients' prognosis was explored via survival analysis. The qRT‐PCR and western blot analysis were used to analyze the FAP mRNA and protein expression levels, respectively. The cell proliferation and apoptosis were determined using the cell counting kit‐8 assay kit and Annexin V‐FITC/PI apoptosis kit, respectively. The HCC patients with FAP overexpression displayed a worse prognosis. The FAP expression was positively associated with the infiltration levels of tumor purity, B cell, CD8 + T cell, CD4 + T cell, macrophage, neutrophil, and dendritic cell. The optimal nine immune related genes were screened between two groups (FAP high vs. low). Moreover, we identified 24 energy metabolism related genes (FAP high vs. low) and these 24 genes were highly expressed in the high FAP expression group. The FAP expression had a significant positive correlation with the expression of PD‐1, CTLA4, PDL‐1, and PDL‐2. The FAP overexpression promoted proliferation and migration while inhibiting the apoptosis of HCC cells. The FAP overexpression promoted the progression of HCC by regulating the immunity to affect the prognosis of HCC patients, thereby serving as a poor prognostic marker for HCC patients.

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Section: Discussionmentioning

confidence: 99%

Section: Fap Overexpression In Cafs Promoted Proliferation and Migrat...mentioning

confidence: 99%

Fibroblast activation protein promotes progression of hepatocellular carcinoma via regulating the immunity

Wang,

Niu,

Yang

et al. 2024

Cell Biology International

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“…MUC1 served as an efficient CAR-T targets and was proved important in breast cancer treatment, so the single resistance to targeted glycosylation (MUC1) is designed to be a kind of CAR-T cell, in xenotransplantation model shows targeted cell toxicity. In vitro studies also have shown that MUC1 has specific cytotoxicity to HCC cell lines, which may be applied to clinical CAR-T therapy for HCC [15].…”

Section: Breakthroughs Of Car-t Therapy In Solid Tumormentioning

confidence: 99%

Difficulties and advance of CAR-T therapy in hepatocellular carcinoma

Zhu

2023

Second International Conference on Biological Engineering and Medical Science (ICBioMed 2022)

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Primary hepatic carcinoma belongs to the malignant tumors that appear most commonly in the world, among which hepatocellular carcinoma (HCC) accounts for 85%-90%, with high frequency and mortality. At present, the main treatment for liver cancer still focuses on surgical resection or transplantation. However, due to its poor recovery and easy recurrence and metastasis, it is necessary to find other adjuvant therapies based on surgical treatment to try to cure primary liver cancer. Chimeric Antigen Receptor -T cell (CAR-T) therapy is emerging immunotherapy in recent years. Constructing specific CAR structures in vitro, then directing T cells to recognize antigen in vivo, while a variety of effectors can be released to kill tumor cells through immune action. Among them, CAR-T therapy has achieved great success dealing with hematological tumors. Nevertheless, because of the heterogeneity and tumor microenvironment (TME) of solid tumors, it's difficult to use CAR-T therapy effectively in clinical treatment. Therefore, here we summarize the problems CAR-T therapy facing in curing HCC, as well as some solutions and breakthroughs, hoping to play a certain role in further applying CAR-T therapy in HCC clinical treatment in the future.

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“…3). For example, CAR-T cells targeting AFP, EGFRvIII, B7H3, EpCAM, MUC1, NKG2DL, PD-L1, and CD147 were demonstrated in preclinical studies [189,[284][285][286][287][288][289]. Many clinical trials for these targets have also been registered and conducted.…”

Section: Liver Cancermentioning

confidence: 99%

Tumor buster - where will the CAR-T cell therapy ‘missile’ go?

Zhang

Cao

et al. 2022

Mol Cancer

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Chimeric antigen receptor (CAR) T cell (CAR-T cell) therapy based on gene editing technology represents a significant breakthrough in personalized immunotherapy for human cancer. This strategy uses genetic modification to enable T cells to target tumor-specific antigens, attack specific cancer cells, and bypass tumor cell apoptosis avoidance mechanisms to some extent. This method has been extensively used to treat hematologic diseases, but the therapeutic effect in solid tumors is not ideal. Tumor antigen escape, treatment-related toxicity, and the immunosuppressive tumor microenvironment (TME) limit their use of it. Target selection is the most critical aspect in determining the prognosis of patients receiving this treatment. This review provides a comprehensive summary of all therapeutic targets used in the clinic or shown promising potential. We summarize CAR-T cell therapies’ clinical trials, applications, research frontiers, and limitations in treating different cancers. We also explore coping strategies when encountering sub-optimal tumor-associated antigens (TAA) or TAA loss. Moreover, the importance of CAR-T cell therapy in cancer immunotherapy is emphasized.

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Transforming primary human hepatocytes into hepatocellular carcinoma with genetically defined factors

Cited by 10 publications

References 76 publications

Fibroblast activation protein promotes progression of hepatocellular carcinoma via regulating the immunity

Fibroblast activation protein promotes progression of hepatocellular carcinoma via regulating the immunity

Difficulties and advance of CAR-T therapy in hepatocellular carcinoma

Tumor buster - where will the CAR-T cell therapy ‘missile’ go?

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