Tumor associated macrophages in esophageal squamous carcinoma: Promising therapeutic implications

Zhang, Jiale; Dong, Yanxin; Di, Shouyin; Xie, Shun; Fan, Boshi; Gong, Taiqian

doi:10.1016/j.biopha.2023.115610

Cited by 5 publications

(1 citation statement)

References 116 publications

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“…The majority of TAMs in the TME of solid tumors, including ESCC [ 12 ], predominantly exhibit M2-like characteristics [ 13 ]. The substantial infiltration of M2 TAMs at tumor sites is closely associated with histological grade, tumor invasion depth, vascular infiltration, lymph node metastasis, clinical stage, and poor prognosis in patients with ESCC [ 14 , 15 ]. Hence, identifying novel biomarkers that can induce TAM reprogramming within the ESCC TME represents a promising therapeutic avenue.…”

Section: Introductionmentioning

confidence: 99%

LINC00330/CCL2 axis-mediated ESCC TAM reprogramming affects tumor progression

Zhao,

Wang,

et al. 2024

Cell Mol Biol Lett

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Background Tumor-associated macrophages (TAMs) significantly influence the progression, metastasis, and recurrence of esophageal squamous cell carcinoma (ESCC). The aberrant expression of long noncoding RNAs (lncRNAs) in ESCC has been established, yet the role of lncRNAs in TAM reprogramming during ESCC progression remains largely unexplored. Methods ESCC TAM-related lncRNAs were identified by intersecting differentially expressed lncRNAs with immune-related lncRNAs and performing immune cell infiltration analysis. The expression profile and clinical relevance of LINC00330 were examined using the TCGA database and clinical samples. The LINC00330 overexpression and interference sequences were constructed to evaluate the effect of LINC00330 on ESCC progression. Single-cell sequencing data, CIBERSORTx, and GEPIA were utilized to analyze immune cell infiltration within the ESCC tumor microenvironment and to assess the correlation between LINC00330 and TAM infiltration. ESCC-macrophage coculture experiments were conducted to investigate the influence of LINC00330 on TAM reprogramming and its subsequent effect on ESCC progression. The interaction between LINC00330 and C–C motif ligand 2 (CCL2) was confirmed through transcriptomic sequencing, subcellular localization analysis, RNA pulldown, silver staining, RNA immunoprecipitation, and other experiments. Results LINC00330 is significantly downregulated in ESCC tissues and strongly associated with poor patient outcomes. Overexpression of LINC00330 inhibits ESCC progression, including proliferation, invasion, epithelial–mesenchymal transition, and tumorigenicity in vivo. LINC00330 promotes TAM reprogramming, and LINC00330-mediated TAM reprogramming inhibits ESCC progression. LINC00330 binds to the CCL2 protein and inhibits the expression of CCL2 and downstream signaling pathways. CCL2 is critical for LINC00330-mediated TAM reprogramming and ESCC progression. Conclusions LINC00330 inhibited ESCC progression by disrupting the CCL2/CCR2 axis and its downstream signaling pathways in an autocrine fashion; and by impeding CCL2-mediated TAM reprogramming in a paracrine manner. The new mechanism of TAM reprogramming mediated by the LINC00330/CCL2 axis may provide potential strategies for targeted and immunocombination therapies for patients with ESCC. Graphical Abstract

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Section: Introductionmentioning

confidence: 99%

LINC00330/CCL2 axis-mediated ESCC TAM reprogramming affects tumor progression

Zhao,

Wang,

et al. 2024

Cell Mol Biol Lett

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Swertianin Promotes Anti-Tumor activity by facilitating Macrophage M1 polarization via STING signaling

Cao,

Hu,

Wang

et al. 2024

International Immunopharmacology

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Multifaceted bioinformatic analysis of m6A‐related ferroptosis and its link with gene signatures and tumour‐infiltrating immune cells in gliomas

Yang,

Hao,

Guiyang

et al. 2024

J Cellular Molecular Medi

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Whether N6‐Methyladenosine (m6A)‐ and ferroptosis‐related genes act on immune responses to regulate glioma progression remains unanswered. Data of glioma and corresponding normal brain tissues were fetched from the TCGA database and GTEx. Differentially expressed genes (DEGs) were identified for GO and KEGG enrichment analyses. The FerrDb database was based to yield ferroptosis‐related DEGs. Hub genes were then screened out using the cytoHubba database and validated in clinical samples. Immune cells infiltrating into the glioma tissues were analysed using the CIBERSORT R script. The association of gene signature underlying the m6A‐related ferroptosis with tumour‐infiltrating immune cells and immune checkpoints in low‐grade gliomas was analysed. Of 6298 DEGs enriched in mRNA modifications, 144 were ferroptosis‐related; NFE2L2 and METTL16 showed the strongest positive correlation. METTL16 knockdown inhibited the migrative and invasive abilities of glioma cells and induced ferroptosis in vitro. NFE2L2 was enriched in the anti‐m6A antibody. Moreover, METTL16 knockdown reduced the mRNA stability and level of NFE2L2 (both p < 0.05). Proportions of CD8+ T lymphocytes, activated mast cells and M2 macrophages differed between low‐grade gliomas and normal tissues. METTL16 expression was negatively correlated with CD8+ T lymphocytes, while that of NFE2L2 was positively correlated with M2 macrophages and immune checkpoints in low‐grade gliomas. Gene signatures involved in the m6A‐related ferroptosis in gliomas were identified via bioinformatic analyses. NFE2L2 interacted with METTL16 to regulate the immune response in low‐grade gliomas, and both molecules may be novel therapeutic targets for gliomas.

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Tumor associated macrophages in esophageal squamous carcinoma: Promising therapeutic implications

Cited by 5 publications

References 116 publications

LINC00330/CCL2 axis-mediated ESCC TAM reprogramming affects tumor progression

LINC00330/CCL2 axis-mediated ESCC TAM reprogramming affects tumor progression

Swertianin Promotes Anti-Tumor activity by facilitating Macrophage M1 polarization via STING signaling

Multifaceted bioinformatic analysis of m6A‐related ferroptosis and its link with gene signatures and tumour‐infiltrating immune cells in gliomas

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