TREM2+ macrophages suppress CD8+ T-cell infiltration after transarterial chemoembolisation in hepatocellular carcinoma

Tan, Jizhou; Fan, Wenzhe; Liu, Ting; Zhu, Bowen; Liu, Yafang; Wang, Shutong; Wu, Jian; Li, Jun; Zou, Fan; Wei, Jialiang; Liu, Lingwei; Zhang, Xiaokai; Liu, Sian; Wang, Yi; Lin, Haibiao; Huang, Xianzhang; Chen, Songling; Li, Jiaping

doi:10.1016/j.jhep.2023.02.032

Cited by 27 publications

(15 citation statements)

References 46 publications

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“…BBB integrity was impaired among Trem2-KO mice Clinical Trem2 loss-of-function mutations have been clearly shown to increase the risk of AD, and microglia are the only cells in the CNS known to express TREM2. We therefore used a Trem2-KO mouse line 29 to investigate the impacts of disrupted TREM2 function on BBB integrity (Supplementary Fig. 1a).…”

Section: Resultsmentioning

confidence: 99%

“…To explore the mechanism of CLDN5 loss in Trem2-KO mice, we reanalyzed publicly available RNAsequencing datasets generated from the microglia of Trem2-KO and WT mice 29 . Gene Ontology (GO) annotation analysis revealed enrichment of pathways related to endothelial cell growth and proliferation among genes upregulated in Trem2-KOs.…”

Section: Ccl2 Upregulation In the Microglia Of Trem2-ko Mice Occurred...mentioning

confidence: 99%

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Loss of TREM2 function in mice leads to blood-brain barrier impairment, pathological leakage, and cognitive deficits due to microglial CCL2 upregulation

Tang,

Yang,

Yin

et al. 2024

Preprint

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Blood-brain barrier (BBB) impairment, which causes leakage of harmful peripheral substances into the brain, is an early indicator of Alzheimer’s disease (AD). Microglia are known to regulate BBB integrity, but the underlying mechanisms of this process remain unclear. We here analyzed BBB permeability and structural integrity in mice. Loss of TREM2 function was found to impair the structural integrity of the BBB; TREM2-deficient microglia showed CCL2 upregulation via activation of the NFκB pathway. The CCL2-CCR2 axis reduced the expression of endothelial tight junction proteins, including claudin-5, occludin, and ZO-1. BBB impairment led to increased leakage of amyloid β (Aβ) and β2-microglobulin (β2M) from peripheral tissues into the brain parenchyma, accelerating the formation of Aβ plaques and subsequent cognitive decline. Importantly, pharmacological blocking of CCR2 restored the BBB integrity, prevented peripheral Aβ deposition in the brain, and improved cognitive function in Trem2-knockout mice. Collectively, these results suggested that loss of TREM2 function induced BBB impairment and accelerated AD progression. Our study thus establishes TREM2 as a critical target for future studies of treatments to prevent and mitigate the effects of AD.

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Section: Resultsmentioning

confidence: 99%

Section: Ccl2 Upregulation In the Microglia Of Trem2-ko Mice Occurred...mentioning

confidence: 99%

Loss of TREM2 function in mice leads to blood-brain barrier impairment, pathological leakage, and cognitive deficits due to microglial CCL2 upregulation

Tang,

Yang,

Yin

et al. 2024

Preprint

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“…The tumor‐infiltrating CD8 + T cells were related to a better prognosis, and Treg were correlated with a worse prognosis of HCC patients (Itoh et al, 2020; Lim et al, 2019). The number of CD8+Tcells were reduced in the posttransarterial chemoembolization microenvironment (Tan et al, 2023). Tumor‐associated macrophages (TAMs) were usually divided into two types, M1 and M2.…”

Section: Discussionmentioning

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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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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“…Further evidence was supplied by several attempts. The scRNA‐seq results on HBV‐HCC tumor tissue revealed that intratumoral cytotoxic T cells (CTL) are predominantly in exhaustion 87,88 . In parallel, these tumor‐specific CD8 + T cells exhibit distinct exhaustion status in true and de novo HBV‐HCC recurrences.…”

Section: Novel Insights From Single‐cell Sequencing In Hbv‐associated...mentioning

confidence: 99%

“…These infiltrating TAMs engaged in modifying the immunosuppressive environment through the TIGIT‐NECTIN2 axis to inhibit T cells' infiltration in HBV‐HCC tumors 74 . Also, a subset of TREM2 + TAMs characterized by more secretion of galectin‐1 was identified to suppress CD8 + T cell infiltration 88 . Furthermore, these immune subsets displayed considerable spatiotemporal heterogeneity and plasticity, exhibiting tissue‐specific preferences.…”

Section: Novel Insights From Single‐cell Sequencing In Hbv‐associated...mentioning

confidence: 99%

Novel insights into HBV‐hepatocellular carcinoma at single‐cell sequencing

Yin,

Zhou,

Xia

et al. 2023

MedComm – Oncology

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A significant proportion of hepatocellular carcinoma (HCC) is pathologically associated with hepatitis B virus (HBV) infection, followed by unsatisfied clinical outcomes. The increasing unmet need for HBV‐associated hepatocellular carcinoma (HBV‐HCC) treatment drives to deeper understand the role of the intricate immune microenvironment, tumor cell plasticity and dynamics of tumor evolution in HBV‐associated hepatic carcinogenesis. Thus, a comprehensive understanding of cross‐talk between HBV, host cells, and tumor microenvironment is of fundamental importance for identifying immune imbalance and heterogeneity in HBV‐HCC. Over the past 5 years, the application of single‐cell RNA sequencing (scRNA‐seq) in the understanding of heterogeneity and dynamics of immune cells, clonal evolution, and cancer stem cell (CSC) subsets of tumor cells has established a landscape for HBV‐HCC tumor ecosystem. Novel insights into anatomizing immune escape mechanisms and tumor drug resistance have remarkably facilitated the revolution of HBV‐HCC clinical treatment. Here, we provided a summary of HCC at single‐cell resolution and details on the basic workflow, limitations, and improvements of scRNA‐seq. The review highlights novel insights derived from scRNA‐seq on advances in the immune microenvironment and tumor heterogeneity of HBV‐HCC.

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TREM2+ macrophages suppress CD8+ T-cell infiltration after transarterial chemoembolisation in hepatocellular carcinoma

Cited by 27 publications

References 46 publications

Loss of TREM2 function in mice leads to blood-brain barrier impairment, pathological leakage, and cognitive deficits due to microglial CCL2 upregulation

Loss of TREM2 function in mice leads to blood-brain barrier impairment, pathological leakage, and cognitive deficits due to microglial CCL2 upregulation

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

Novel insights into HBV‐hepatocellular carcinoma at single‐cell sequencing

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