Related Experiment Video
Updated: Mar 5, 2026
Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
Published on: January 18, 2017
STAT3 and NF-κB are Simultaneously Suppressed in Dendritic Cells in Lung Cancer
Rui Li1,2, Fang Fang1,2, Ming Jiang1,2
1The CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Abstract:
Tumour-induced dendritic cell (DC) dysfunction plays an important role in cancer immune escape. However, the underlying mechanisms are not yet fully understood, reflecting the lack of appropriate experimental models both in vivo and in vitro. In the present study, an in vitro study model for tumour-induced DC dysfunction was established by culturing DCs with pooled sera from multiple non-small cell lung cancer (NSCLC) patients. The results demonstrated that tumour-induced human monocyte-derived DCs exhibited systematic functional deficiencies. Transcriptomics analysis revealed that the expression of major functional cluster genes, including the MHC class II family, cytokines, chemokines, and co-stimulatory molecules, was significantly altered in tumour-induced DCs compared to that in control cells. Further examination confirmed that both NF-κB and STAT3 signalling pathways were simultaneously repressed by cancer sera, suggesting that the attenuated NF-κB and STAT3 signalling could be the leading cause of DC dysfunction in cancer. Furthermore, reversing the deactivated NF-κB and STAT3 signalling could be a strategy for cancer immunotherapy.
Insights
Tumour-induced dysfunction in dendritic cells (DCs) hinders cancer immunity. This study establishes an in vitro model showing cancer sera impair DC function by repressing NF-κB and STAT3 signaling, offering a potential immunotherapy target.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Tumour-induced dendritic cell (DC) dysfunction is a key mechanism in cancer immune evasion.
- Understanding the molecular mechanisms of DC dysfunction requires robust experimental models.
- Existing in vivo and in vitro models are insufficient to fully elucidate these mechanisms.
Purpose of the Study:
- To establish an in vitro model for studying tumour-induced DC dysfunction.
- To investigate the molecular alterations in DCs exposed to non-small cell lung cancer (NSCLC) sera.
- To identify the signalling pathways responsible for DC functional impairment in cancer.
Main Methods:
- An in vitro model was developed by co-culturing human monocyte-derived dendritic cells (DCs) with pooled sera from NSCLC patients.
- Transcriptomic analysis was performed to assess gene expression changes in DCs.
- Western blotting or similar techniques were used to examine the activation status of key signalling pathways like NF-κB and STAT3.
Main Results:
- Tumour-induced DCs exhibited significant functional deficiencies.
- Gene expression profiling revealed altered expression of key functional genes, including MHC class II, cytokines, chemokines, and co-stimulatory molecules.
- Cancer sera were found to simultaneously repress both NF-κB and STAT3 signalling pathways in DCs.
Conclusions:
- Repression of NF-κB and STAT3 signalling pathways is a primary cause of tumour-induced DC dysfunction.
- The established in vitro model effectively mimics DC impairment seen in cancer patients.
- Restoring NF-κB and STAT3 signalling presents a potential therapeutic strategy for cancer immunotherapy.
