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Updated: Jul 1, 2025

Macrophage Differentiation and Polarization into an M2-Like Phenotype using a Human Monocyte-Like THP-1 Leukemia Cell Line
Published on: August 2, 2021
Nocardia rubra cell wall skeleton regulates tumour-associated macrophage polarization by reprogramming M2 macrophages
Wei Chen1, Qianyu Guo1, Yi Zhang2
1Department of Histology and Embryology, Hebei Medical University, Shijiazhuang, China.
Abstract:
Targeted therapy with tumour-associated macrophages (TAMs) has emerged as a new paradigm for immunotherapy of cervical cancer. Nocardia rubra cell wall skeleton (Nr-CWS) for external use is an immunotherapeutic agent. In this study, we aimed to explore the effects of Nr-CWS on TAMs and the potential mechanisms. Cervical tissue samples were collected before and after Nr-CWS treatment from patients with high-risk HPV infection and cervical intraepithelial neoplasia (CIN). The effect of Nr-CWS on macrophages in vivo was examined by immunohistochemistry and double-labeling immunofluorescence histochemistry. In vitro experiments were performed using a TAM model established by THP-1 cells under Nr-CWS treatment. We found that Nr-CWS treatment significantly reduced the numbers of total macrophages and M2 macrophages, increased the proportion of M1 macrophages and decreased the proportion of M2 macrophages in cervical tissues. After Nr-CWS treatment in vitro, the expression levels of the M1 macrophage markers were increased, while the expression levels of the M2 macrophage markers were decreased. Nr-CWS treatment also activated STAT1 pathways but inhibited STAT6 pathways. These results indicated that Nr-CWS may improve local immune response and reverse immunosuppression by regulating the M2 to M1 polarization of TAMs via STAT1/STAT6 pathways.
Insights
Nocardia rubra cell wall skeleton (Nr-CWS) therapy effectively targets tumour-associated macrophages (TAMs) in cervical cancer. Nr-CWS promotes M1 macrophage polarization and inhibits M2 macrophages, potentially reversing immunosuppression.
Area of Science:
- Immunology
- Oncology
- Microbiology
Background:
- Tumour-associated macrophages (TAMs) play a crucial role in cervical cancer progression and immune evasion.
- Targeting TAMs represents a promising strategy for cervical cancer immunotherapy.
- Nocardia rubra cell wall skeleton (Nr-CWS) is an immunotherapeutic agent with potential anti-tumour effects.
Purpose of the Study:
- To investigate the effects of Nr-CWS on TAMs in cervical cancer.
- To elucidate the underlying mechanisms of Nr-CWS action on macrophage polarization.
- To assess the potential of Nr-CWS in reversing the immunosuppressive tumour microenvironment.
Main Methods:
- Cervical tissue samples from patients with high-risk HPV and CIN were analyzed before and after Nr-CWS treatment.
- In vivo studies utilized immunohistochemistry and immunofluorescence to assess macrophage populations.
- In vitro experiments established a TAM model using THP-1 cells treated with Nr-CWS.
Main Results:
- Nr-CWS treatment significantly reduced total and M2 macrophage numbers in cervical tissues.
- A notable increase in M1 macrophage proportion and a decrease in M2 proportion were observed post-Nr-CWS treatment.
- In vitro, Nr-CWS upregulated M1 markers, downregulated M2 markers, activated STAT1, and inhibited STAT6 pathways.
Conclusions:
- Nr-CWS effectively modulates TAM polarization from an immunosuppressive M2 phenotype to an anti-tumour M1 phenotype.
- The STAT1/STAT6 signaling pathways are implicated in Nr-CWS-mediated M2 to M1 macrophage polarization.
- Nr-CWS holds potential for improving local immune responses and overcoming immunosuppression in cervical cancer.
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