The Role of Tumor Microenvironment in Invasion and Metastasis of Esophageal Squamous Cell Carcinoma

Zheng, Shuyue; Liu, Beilei; Guan, Xin‐Yuan

doi:10.3389/fonc.2022.911285

Cited by 7 publications

(2 citation statements)

References 157 publications

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“…Recent studies have increasingly demonstrated that the tumor microenvironment (TME) is pivotal in the progression of malignancies, including ESCC [ 5 , 6 ]. Tumor-associated macrophages (TAMs) are prevalent immune cell infiltrates within the TME and play pivotal roles in tumor progression, metastasis, recurrence and immune evasion [ 7 – 9 ].…”

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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“…The immunosuppressive microenvironment is important in promoting tumor growth and metastasis in ESCC. 2 Regulatory T (Treg) cells play a critical role in immune suppression in the tumor microenvironment; however, their function in ESCC is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Lymphatic endothelial cell-mediated accumulation of CD177 ⁺ Treg cells suppresses antitumor immunity in human esophageal squamous cell carcinoma

Ma,

Li,

Yang

et al. 2024

OncoImmunology

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Regulatory T (Treg) cells are critical in shaping an immunosuppressive microenvironment to favor tumor progression and resistance to therapies. However, the heterogeneity and function of Treg cells in esophageal squamous cell carcinoma (ESCC) remain underexplored. We identified CD177 as a tumor-infiltrating Treg cell marker in ESCC. Interestingly, expression levels of CD177 and PD-1 were mutually exclusive in tumor Treg cells. CD177 + Treg cells expressed high levels of IL35, in association with CD8 + T cell exhaustion, whereas PD-1 + Treg cells expressed high levels of IL10. Pan-cancer analysis revealed that CD177 + Treg cells display increased clonal expansion compared to PD-1 + and double-negative (DN) Treg cells, and CD177 + and PD-1 + Treg cells develop from the same DN Treg cell origin. Importantly, we found CD177 + Treg cell infiltration to be associated with poor overall survival and poor response to anti-PD-1 immunotherapy plus chemotherapy in ESCC patients. Finally, we found that lymphatic endothelial cells are associated with CD177 + Treg cell accumulation in ESCC tumors, which are also decreased after anti-PD-1 immunotherapy plus chemotherapy. Our work identifies CD177 + Treg cell as a tumor-specific Treg cell subset and highlights their potential value as a prognostic marker of survival and response to immunotherapy and a therapeutic target in ESCC.

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Single‐cell transcriptome sequencing analysis reveals intra‐tumor heterogeneity in esophageal squamous cell carcinoma

Nie,

Yao,

Wei

et al. 2024

Environmental Toxicology

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Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor of the digestive system that poses a significant threat to human life and health. It is crucial to thoroughly investigate the mechanisms of esophageal carcinogenesis and identify potential key molecular events in its carcinogenesis. Single‐cell transcriptome sequencing is an emerging technology that has gained prominence in recent years for studying molecular mechanisms, which may help to further explore the underlying mechanisms of the ESCC tumor microenvironment in depth. The single‐cell dataset was obtained from GSE160269 in the Gene Expression Omnibus database, including 60 tumor samples and four paracancer samples. The single‐cell data underwent dimensional reduction clustering analysis to identify clusters and annotate expression profiles. Subcluster analysis was conducted for each cellular taxon. Copy number variation analysis of tumor cell subpopulations was performed to primarily identify malignant cells within them. A proposed chronological analysis was performed to obtain the process of cell differentiation. In addition, cell communication, transcription factor analysis, and tumor pathway analysis were also performed. Relevant risk models and key genes were established by univariate COX regression and LASSO analysis. The key genes obtained from the screen were subjected to appropriate silencing and cellular assays, including CCK‐8, 5‐ethynyl‐2′‐deoxyuridine, colony formation, and western blot. Single‐cell analysis revealed that normal samples contained a large number of fibroblasts, T cells, and B cells, with fewer other cell types, whereas tumor samples exhibited a relatively balanced distribution of cell types. Subclassification analysis of immune cells, fibroblasts, endothelial cells, and epithelial cells revealed their specific spatial characteristics. The prognostic risk model, we constructed successfully, achieved accurate prognostic stratification for ESCC patients. The screened key gene, UPF3A, was found to be significantly associated with the development of ESCC by cellular assays. This process might be linked to the phosphorylation of ERK and P38. Single‐cell transcriptome analysis successfully revealed the distribution of cell types and major expressed factors in ESCC patients, which could facilitate future in‐depth studies on the therapeutic mechanisms of ESCC.

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The Role of Tumor Microenvironment in Invasion and Metastasis of Esophageal Squamous Cell Carcinoma

Cited by 7 publications

References 157 publications

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

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

Lymphatic endothelial cell-mediated accumulation of CD177 ⁺ Treg cells suppresses antitumor immunity in human esophageal squamous cell carcinoma

Single‐cell transcriptome sequencing analysis reveals intra‐tumor heterogeneity in esophageal squamous cell carcinoma

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The Role of Tumor Microenvironment in Invasion and Metastasis of Esophageal Squamous Cell Carcinoma

Cited by 7 publications

References 157 publications

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

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

Lymphatic endothelial cell-mediated accumulation of CD177 + Treg cells suppresses antitumor immunity in human esophageal squamous cell carcinoma

Single‐cell transcriptome sequencing analysis reveals intra‐tumor heterogeneity in esophageal squamous cell carcinoma

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Lymphatic endothelial cell-mediated accumulation of CD177 ⁺ Treg cells suppresses antitumor immunity in human esophageal squamous cell carcinoma