Application of adoptive cell therapy in hepatocellular carcinoma

Wu, Dengqiang; Li, Yujie

doi:10.1111/imm.13677

Cited by 13 publications

(9 citation statements)

References 158 publications

(167 reference statements)

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“…TILs frequently contain T cells, B cells, and natural killer (NK) cells, which are one of the exemplary elements of the host anticancer immune responses [ 31 , 32 ]. The international TILs Working Group’s standards included a standardized TIL scoring system, and the average TIL score based on the entire stromal surface as opposed to hotspots showed significant clinical relevance in cancer detection [ 33 , 34 ]. The role of FIGN in controlling immunological response, however, has not yet been documented.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive characterization of Fidgetin on tumor immune microenvironment evaluation and immunotherapy in human hepatocellular carcinoma

Qi,

Chen,

Liao

et al. 2024

Aging

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Most cancers have a downregulation of Fidgetin (FIGN), which has been linked to tumor growth. However, there aren’t many papers that mention FIGN’s connection to hepatocellular carcinoma (HCC). Here, FIGN expression in HCC tissues was markedly reduced as compared to nearby normal liver tissues. According to univariate and multivariate Cox regression, it served as an independent predictor of survival outcomes. Patients with high levels of FIGN expression had a worse outcome. FIGN was shown to be engaged in immune-related pathways and to have a positive correlation with immunological score and immune cells according to KEGG pathway analysis. In HCC patients, FIGN was substantially linked with immunological checkpoints and the hot tumor state. Additionally, immunotherapy and chemotherapy showed a significant therapeutic response in HCC patients with low FIGN expression. This research revealed that FIGN expression was tightly related to hepatoma immunity and might be employed as a biomarker to predict patient prognosis and guide medication.

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Section: Discussionmentioning

confidence: 99%

Comprehensive characterization of Fidgetin on tumor immune microenvironment evaluation and immunotherapy in human hepatocellular carcinoma

Qi,

Chen,

Liao

et al. 2024

Aging

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“…Despite their efficacy, drug resistance to ICIs in treating HCC is prevalent, often due to various factors like deficient antitumor T cells and impaired memory T cells formation ( 7 ). The field of adoptive cell therapy (ACT) encompasses three primary modalities: tumor-infiltrating lymphocytes (TIL), genetically engineered T cell receptor (TCR), and chimeric antigen receptor (CAR) T cells ( 8 , 9 ).In contrast to ICI, which inhibits T-cell suppressor receptors, ACT relies on in vitro culture and expansion of genetically modified or engineered T cells, thereby enhancing T-cell specificity ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

Key oncogenic signaling pathways affecting tumor-infiltrating lymphocytes infiltration in hepatocellular carcinoma: basic principles and recent advances

Wang,

Yuan,

et al. 2024

Front. Immunol.

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The incidence of hepatocellular carcinoma (HCC) ranks first among primary liver cancers, and its mortality rate exhibits a consistent annual increase. The treatment of HCC has witnessed a significant surge in recent years, with the emergence of targeted immune therapy as an adjunct to early surgical resection. Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has shown promising results in other types of solid tumors. This article aims to provide a comprehensive overview of the intricate interactions between different types of TILs and their impact on HCC, elucidate strategies for targeting neoantigens through TILs, and address the challenges encountered in TIL therapies along with potential solutions. Furthermore, this article specifically examines the impact of oncogenic signaling pathways activation within the HCC tumor microenvironment on the infiltration dynamics of TILs. Additionally, a concise overview is provided regarding TIL preparation techniques and an update on clinical trials investigating TIL-based immunotherapy in solid tumors.

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“…Immunotherapy, including immune-checkpoint inhibitors (ICIs) and adoptive cell therapy (ACT), has revolutionized the clinical management of various tumors and offers novel prospects for HCC treatment [ 5 , 6 ]. However, the application of ICIs in HCC therapy presents challenges, as the majority of patients exhibit limited responsiveness to ICIs, either as monotherapy or in combination regimens, owing to a low response rate and the occurrence of severe immune-related adverse events [ 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Atovaquone enhances antitumor efficacy of TCR-T therapy by augmentation of ROS-induced ferroptosis in hepatocellular carcinoma

Chen,

Yu,

et al. 2024

Cancer Immunol Immunother

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T-cell receptor (TCR) engineered T-cell therapy has recently emerged as a promising adoptive immunotherapy approach for tumor treatment, yet hindered by tumor immune evasion resulting in poor therapeutic efficacy. The introduction of ferroptosis-targeted inducers offers a potential solution, as they empower T cells to induce ferroptosis and exert influence over the tumor microenvironment. Atovaquone (ATO) stands as a prospective pharmaceutical candidate with the potential to target ferroptosis, effectively provoking an excessive generation and accumulation of reactive oxygen species (ROS). In this study, we evaluated the effectiveness of a combination therapy comprising ATO and TCR-T cells against hepatocellular carcinoma (HCC), both in vitro and in vivo. The results of lactate dehydrogenase and cytokine assays demonstrated that ATO enhanced cytotoxicity mediated by AFP-specific TCR-T cells and promoted the release of IFN-γ in vitro. Additionally, in an established HCC xenograft mouse model, the combined therapy with low-dose ATO and TCR-T cells exhibited heightened efficacy in suppressing tumor growth, with no apparent adverse effects, comparable to the results achieved through monotherapy. The RNA-seq data unveiled a significant activation of the ferroptosis-related pathway in the combination therapy group in comparison to the TCR-T cells group. Mechanistically, the synergy between ATO and TCR-T cells augmented the release of IFN-γ by TCR-T cells, while concurrently elevating the intracellular and mitochondrial levels of ROS, expanding the labile iron pool, and impairing the integrity of the mitochondrial membrane in HepG2 cells. This multifaceted interaction culminated in the potentiation of ferroptosis within the tumor, primarily induced by an excess of ROS. In summary, the co-administration of ATO and TCR-T cells in HCC exhibited heightened vulnerability to ferroptosis. This heightened susceptibility led to the inhibition of tumor growth and the stimulation of an anti-tumor immune response. These findings suggest that repurposing atovaquone for adoptive cell therapy combination therapy holds the potential to enhance treatment outcomes in HCC.

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Application of adoptive cell therapy in hepatocellular carcinoma

Cited by 13 publications

References 158 publications

Comprehensive characterization of Fidgetin on tumor immune microenvironment evaluation and immunotherapy in human hepatocellular carcinoma

Comprehensive characterization of Fidgetin on tumor immune microenvironment evaluation and immunotherapy in human hepatocellular carcinoma

Key oncogenic signaling pathways affecting tumor-infiltrating lymphocytes infiltration in hepatocellular carcinoma: basic principles and recent advances

Atovaquone enhances antitumor efficacy of TCR-T therapy by augmentation of ROS-induced ferroptosis in hepatocellular carcinoma

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