Tumour‐associated macrophages in gastric cancer: From function and mechanism to application

Li, Jie; Sun, Juan; Zeng, Ziyang; Liu, Zhen; Ma, Mingwei; Zheng, Zicheng; He, Yixuan; Kang, Weiming

doi:10.1002/ctm2.1386

Cited by 7 publications

(3 citation statements)

References 173 publications

(472 reference statements)

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“…Previous studies have shown that infiltration of naive B cells in GC is associated with an unfavorable prognosis 34 . It is widely acknowledged that excessive activation of M2 macrophages can contribute to fibrosis during tissue healing and possibly encourage tumor development via immunosuppression 35 . In this research, we investigated the positive correlation between the expression of naive B cells and TIE1, and we further observed higher levels of M2 macrophages and lower levels of M1 macrophages in GC patients with elevated TIE1 expression.…”

Section: Discussionmentioning

confidence: 99%

Identification of the Expression of TIE1 and Its Mediated Immunosuppression in Gastric Cancer

Gong,

Zheng,

et al. 2024

J. Cancer

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Background: Recently, various evidence has confirmed that Tyrosine Kinase with Immunoglobulin-like and EGF-like domains 1 (TIE1) promotes tumor growth in many cancers. However, the precise mechanism underlying TIE1's involvement in Gastric Cancer (GC) remains elusive. This research aimed to investigate the biological function of TIE1 in regulating GC progression. Methods: The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), GEPIA2.0, Sangerbox3.0 and TIMER databases were used to analyze the TIE1 expression. Immunohistochemistry (IHC) was used to demonstrate the expression of TIE1. TCGA, GEPIA2.0 and Kaplan-Meier were utilized for survival analysis and to explore the association of TIE1 with clinicopathological features. Protein-Protein Interaction (PPI) networks were constructed using Cytoscape. The potential molecular mechanism of TIE1 was investigated by Gene Ontology (GO), Kyoto Encyclopedia of Gene Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA). We studied the relationships between TIE1 and mutations, immune checkpoints (ICs), tumor mutational burden (TMB), as well as microsatellite instability (MSI) to explore the underlying mechanism of immunity in GC. Results: Compared with normal tissue, TIE1 was significantly overexpressed in GC tissues (p = 0.0072) and was associated with poor survival (P < 0.05). According to GO and KEGG enrichment analyses, TIE1 was enriched in signal pathways related to the occurrence, invasion, and migration of malignant tumors (i.e., PI3K-Akt signaling pathway, Calcium signaling pathway, etc.). Immune infiltration analysis suggested that TIE1 is positively correlated with macrophages M2 and negatively correlated with Mast cells, naive B cells and Follicular helper T cells (TFH), which may be a contributing factor to tumor progression. Furthermore, the research on the tumor microenvironment (TME) and tumor purity also proved that TIE1 may be an oncogene. Mutation analysis showed that the high expression group of TIE1 had a higher frequency of mutations in TP53 and ARID1, while the TMB score was lower. Conclusion: TIE1 might be an oncogene via regulating dysregulated immune infiltration to cause immunosuppression in GC and could be identified as a biomarker for prognosis and a therapeutic target for GC.

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Section: Discussionmentioning

confidence: 99%

Identification of the Expression of TIE1 and Its Mediated Immunosuppression in Gastric Cancer

Gong,

Zheng,

et al. 2024

J. Cancer

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“…TAMs-targeted treatment is an optimizing strategy to improve the therapeutic effect of anti-tumor immunotherapy. [71][72][73][74] In this section, we discussed the effects of PDE5 inhibitors on macrophages in TME (Table 2). 67,68,69 The effects of PDE5 inhibitors depend on the different polarization status of macrophages.…”

Section: Macrophagesmentioning

confidence: 99%

PDE5 inhibitors against cancer via mediating immune cells in tumor microenvironment: AI‐based approach for future drug repurposing exploration

Zhang,

Huang,

Feng

et al. 2024

Interdisciplinary Medicine

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Phosphodiesterase‐5 (PDE5) inhibitors are used clinically for the treatment of erectile dysfunction, pulmonary arterial hypertension, and other urological diseases. Emerging evidences have suggested the therapeutic capacity of PDE5 inhibitors as the repurposed drugs in oncology. However, the essential immune function of PDE5 inhibitors against cancer in tumor microenvironment (TME) remains unclear. This review aimed to summarize the recent advances regarding the repurposing of PDE5 inhibitors as anti‐cancer agents for cancer management to enhance the anti‐tumor immune response by mediating various immune cells, which included the myeloid‐derived suppressor cells, macrophages, T cells, fibroblasts, and natural killer cells in TME. Moreover, artificial intelligence (AI), as a new approach, is composed of traditional machine learning and deep learning methods and could be potentially used to identify the targets of immune cells in TME and predict the efficacy for repurposed drug toward malignancies. In summary, these endeavors provide novel insights into the comprehensive strategies for PDE5 inhibitors mediating immune cells against cancer and AI‐based approach for future drug repurposing exploration.

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“…Gastric carcinoma is the third deadliest type of cancer [4]. Its pathogenesis is complex and closely related to age, high salt intake and a lack of fruit and vegetables.…”

Section: Introductionmentioning

confidence: 99%

Anti-Tumor Effects and Toxicity Reduction Mechanisms of Prunella vulgaris: A Comprehensive Review

Ning,

Nan,

Chen

et al. 2024

Molecules

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Purpose: To investigate and systematically describe the mechanism of action of Prunella vulgaris (P. vulgaris) against digestive system tumors and related toxicity reduction. Methods: This study briefly describes the history of medicinal food and the pharmacological effects of P. vulgaris, focusing on the review of the anti-digestive tumor effects of the active ingredients of P. vulgaris and the mechanism of its toxicity reduction. Results: The active ingredients of P. vulgaris may exert anti-tumor effects by inducing the apoptosis of cancer cells, inhibiting angiogenesis, inhibiting the migration and invasion of tumor cells, and inhibiting autophagy. In addition, P. vulgaris active ingredients inhibit the release of inflammatory factors and macrophages and increase the level of indicators of oxidative stress through the modulation of target genes in the pathway to achieve the effect of toxicity reduction. Conclusion: The active ingredients in the medicine food homology plant P. vulgaris not only treat digestive system tumors through different mechanisms but also reduce the toxic effects. P. vulgaris is worthy of being explored more deeply.

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Tumour‐associated macrophages in gastric cancer: From function and mechanism to application

Cited by 7 publications

References 173 publications

Identification of the Expression of TIE1 and Its Mediated Immunosuppression in Gastric Cancer

Identification of the Expression of TIE1 and Its Mediated Immunosuppression in Gastric Cancer

PDE5 inhibitors against cancer via mediating immune cells in tumor microenvironment: AI‐based approach for future drug repurposing exploration

Anti-Tumor Effects and Toxicity Reduction Mechanisms of Prunella vulgaris: A Comprehensive Review

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