Hepatocellular carcinoma-derived FOXO1 inhibits tumor progression by suppressing IL-6 secretion from macrophages

Cui, Xiao; Zhao, Huiyong; Wei, Sheng; Du, Qiang; Dong, Kun; Yan, Yaohua; Geller, David A.

doi:10.1016/j.neo.2023.100900

Cited by 14 publications

(10 citation statements)

References 48 publications

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“…As research deepens, TME is receiving an increasing attention, and for this reason, immunosuppressive therapy has been launched ( Llovet et al, 2022 ). A previous study showed that FOXO1 played a part in macrophages through transcriptionally controlling IRF-1/nitrio oxide (NO) axis and reduced the secretion of IL-6 from macrophages in TME indirectly ( Cui et al, 2023 ). In order to Further explore the relationship between Foxo signaling pathway and TME, we also evaluated the immune landscapes in 3 FMSs molecular subtypes.…”

Section: Discussionmentioning

confidence: 99%

Molecular subtypes and scoring tools related to Foxo signaling pathway for assessing hepatocellular carcinoma prognosis and treatment responsiveness

Tu,

Qiu

2023

Front. Pharmacol.

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Background: Transcription factors in Foxo signaling pathway influence hepatocellular carcinoma metastasis through epithelial mesenchymal transition-related pathways. Prognostic factors in the Foxo signaling pathway are feasible for HCC prognosis and therapeutic management.Methods: Based on the differentially expressed genes and Foxo signaling pathway genes in HCC, the ConsensusClusterPlus package was conducted to identify Foxo signaling pathway-related molecular subtypes in HCC. Based on the DEGs in the FMSs, the optimal prognostic factors in HCC were screened by cox and least absolute shrinkage and selection operator (LASSO) cox analysis to form the Foxo prognosis score (FPS). The prognostic predictive effectiveness of FPS was assessed by Kaplan Meier (K-M) analysis and Receiver Operating Characteristic (ROC) analysis. Additionally, tumor microenvironment (TME) score, tumor mutation burden (TMB) and treatment sensitivity differences in FMSs and FPS groups were also evaluated.Results: There were low, medium and high Foxo signaling pathway activity molecular subtypes in HCC named FMS 1, FMS 2 and FMS 3, respectively. FMS 1 with lowest Foxo signaling pathway activity presented an excellent survival advantage, while FMS 3 with highest Foxo signaling pathway activity exhibited an inhibitory TME status. According to FPS grouping, low FPS exhibited favorable survival, low TMB and anti-tumor activity. Patients in the low FPS group were mostly in the early stage of cancer. Moreover, we found that patients with high and low FPS exhibited different sensitivity to chemotherapy, and patients with low FPS were more sensitive to immunotherapy.Conclusion: We revealed a novel molecular subtype and prognostic tool based on Foxo signaling pathway signature, which could potentially provide a direction for accurate and effective assessment of potential personalized treatment options and prognostic management for HCC patients.

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Section: Discussionmentioning

confidence: 99%

Molecular subtypes and scoring tools related to Foxo signaling pathway for assessing hepatocellular carcinoma prognosis and treatment responsiveness

Tu,

Qiu

2023

Front. Pharmacol.

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“…The transcription factor FOXO1 specifically targets TAMs, leading to a reduction in IL-6 secretion by these macrophages. This inhibition of IL-6/STAT3 signaling pathway effectively hampers HCC progression ( 111 ). Not only does TAM impact other TILs, but it also influences the expression of Tregs in tumors through two pathways: 1) Recruitment of Tregs via secretion of CCL22; and 2) Induction of naïve T-cells to aggregate and differentiate into Tregs (CCL18 and IL-10) ( 112 ).…”

Section: Tumor Infiltrating Lymphocytesmentioning

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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“…The PPAR signaling pathway is crucial for lipid metabolism, including fatty acid uptake and oxidation ( Wei et al, 2010 ; Lakshmi et al, 2017 ; Cui et al, 2023 ). PPAR signaling-regulated FAO can promote cell-mediated ECM degradation, which is countered by profibrotic TGF-β ( Zhao et al, 2019 ).…”

Section: Targeting Metabolic Dysregulation For Fibrosis Therapymentioning

confidence: 99%

Immunometabolism changes in fibrosis: from mechanisms to therapeutic strategies

et al. 2023

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Immune cells are essential for initiating and developing the fibrotic process by releasing cytokines and growth factors that activate fibroblasts and promote extracellular matrix deposition. Immunometabolism describes how metabolic alterations affect the function of immune cells and how inflammation and immune responses regulate systemic metabolism. The disturbed immune cell function and their interactions with other cells in the tissue microenvironment lead to the origin and advancement of fibrosis. Understanding the dysregulated metabolic alterations and interactions between fibroblasts and the immune cells is critical for providing new therapeutic targets for fibrosis. This review provides an overview of recent advances in the pathophysiology of fibrosis from the immunometabolism aspect, highlighting the altered metabolic pathways in critical immune cell populations and the impact of inflammation on fibroblast metabolism during the development of fibrosis. We also discuss how this knowledge could be leveraged to develop novel therapeutic strategies for treating fibrotic diseases.

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Hepatocellular carcinoma-derived FOXO1 inhibits tumor progression by suppressing IL-6 secretion from macrophages

Cited by 14 publications

References 48 publications

Molecular subtypes and scoring tools related to Foxo signaling pathway for assessing hepatocellular carcinoma prognosis and treatment responsiveness

Molecular subtypes and scoring tools related to Foxo signaling pathway for assessing hepatocellular carcinoma prognosis and treatment responsiveness

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

Immunometabolism changes in fibrosis: from mechanisms to therapeutic strategies

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