NOD2 deficiency confers a pro-tumorigenic macrophage phenotype to promote lung adenocarcinoma progression
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Updated: Oct 28, 2025
Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo
Published on: July 20, 2019
Yibei Wang1,2, Ziwei Miao2, Xiaoxue Qin2
1Department of Thoracic Surgery, Shengjing Hospital of China Medical University, Shenyang, China.
Abstract:
Nucleotide-binding and oligomerization domain-containing protein 2 (NOD2) was a member of the NOD-like receptor family and played an important role in the innate immune response. Dysregulated NOD2 had been reported to contribute to tumorigenesis and progression. Here, we investigated that decreased NOD2 expressions could affect the phenotypic polarization of tumour-associated macrophages and thus lead to the poor prognosis of lung adenocarcinoma patients. We clustered the patients by the single-sample gene set enrichment analysis of tumour microenvironment and 13 prognostic differentially expressed immune-related genes (PDEIRGs) were obtained based on prognostic analyses. After multiple assessments on the 13 PDEIRGs, NOD2 was considered to be the central immune gene and had a strong effect on suppressing tumour progression. Decreased NOD2 expression could be induced by cancer cells and lead to the phenotypic polarization of macrophages from protective M1 phenotype to pro-tumorigenic M2 subtype which might be attributed to the down-regulating of NF-κB signalling pathway. This study draw attention to the role of inhibited innate immune function mediated by depletion of NOD2 in the TME. Our work also points to a potential strategy of NOD2-mediated TAM-targeted immunotherapy.
Insights
Decreased Nucleotide-binding and oligomerization domain-containing protein 2 (NOD2) expression in lung adenocarcinoma promotes tumor growth by altering macrophage polarization. Restoring NOD2 function may offer a novel immunotherapy strategy.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Nucleotide-binding and oligomerization domain-containing protein 2 (NOD2) is crucial for innate immunity.
- Aberrant NOD2 expression is linked to cancer development and progression.
- Tumor-associated macrophages (TAMs) play a significant role in the tumor microenvironment (TME).
Purpose of the Study:
- To investigate the impact of decreased NOD2 expression on macrophage polarization in lung adenocarcinoma.
- To identify prognostic immune-related genes associated with lung adenocarcinoma.
- To explore NOD2 as a potential therapeutic target for lung adenocarcinoma immunotherapy.
Main Methods:
- Single-sample gene set enrichment analysis (ssGSEA) of the tumor microenvironment.
- Prognostic analysis to identify 13 prognostic differentially expressed immune-related genes (PDEIRGs).
- Assessment of NOD2's role in macrophage polarization and its association with the NF-κB signaling pathway.
Main Results:
- NOD2 was identified as a central immune gene suppressing tumor progression in lung adenocarcinoma.
- Decreased NOD2 expression, induced by cancer cells, promotes M2 macrophage polarization.
- This polarization shift from M1 to M2 macrophages is potentially mediated by NF-κB pathway downregulation.
- Inhibited innate immune function due to NOD2 depletion in the TME was observed.
Conclusions:
- Reduced NOD2 expression contributes to poor prognosis in lung adenocarcinoma by promoting pro-tumorigenic M2 macrophages.
- NOD2 plays a critical role in regulating macrophage phenotype within the tumor microenvironment.
- Targeting NOD2 presents a promising strategy for developing novel immunotherapies for lung adenocarcinoma.
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