Related Experiment Video
Updated: Jun 21, 2025
Studying the Effects of Tumor-Secreted Paracrine Ligands on Macrophage Activation using Co-Culture with Permeable Membrane Supports
Published on: November 28, 2019
M2-type tumor-associated macrophages upregulated PD-L1 expression in cervical cancer via the PI3K/AKT pathway
Fan Guo1,2, Weina Kong1, Dewei Li3
1Department of Medical Laboratory Center, Tumor Hospital Affiliated to Xinjiang Medical University, State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, No 789 Suzhou Road, Urumqi, 830011, Xinjiang, China.
Background And Purpose:
PD-1/PD-L1 inhibitors have become a promising therapy. However, the response rate is lower than 30% in patients with cervical cancer (CC), which is related to immunosuppressive components in tumor microenvironment (TME). Tumor-associated macrophages (TAMs), as one of the most important immune cells, are involved in the formation of tumor suppressive microenvironment. Therefore, it will provide a theoretical basis for curative effect improvement about the regulatory mechanism of TAMs on PD-L1 expression.
Methods:
The clinical data and pathological tissues of CC patients were collected, and the expressions of PD-L1, CD68 and CD163 were detected by immunohistochemistry. Bioinformatics was used to analyze the macrophage subtypes involved in PD-L1 regulation. A co-culture model was established to observe the effects of TAMs on the morphology, migration and invasion function of CC cells, and the regulatory mechanism of TAMs on PD-L1.
Results:
PD-L1 expression on tumor cells could predict the poor prognosis of patients. And there was a strong correlation between PD-L1 expression with CD163+TAMs infiltration. Similarly, PD-L1 expression was associated with M1/M2-type TAMs infiltration in bioinformatics analysis. The results of cell co-culture showed that M1/M2-type TAMs could upregulate PD-L1 expression, especially M2-type TAMs may elevate the PD-L1 expression via PI3K/AKT pathway. Meanwhile, M1/M2-type TAMs can affect the morphological changes, and enhance migration and invasion abilities of CC cells.
Conclusions:
PD-L1 expression in tumor cells can be used as a prognostic factor and is closely related to CD163+TAMs infiltration. In addition, M2-type TAMs can upregulate PD-L1 expression in CC cells through PI3K/AKT pathway, enhance the migration and invasion capabilities, and affect the tumor progression.
Insights
Tumor-associated macrophages (TAMs), particularly M2-type, enhance PD-L1 expression and promote cervical cancer progression. Targeting TAMs may improve PD-1/PD-L1 inhibitor efficacy in cervical cancer treatment.
Area of Science:
- Immunology
- Oncology
- Molecular Biology
Background:
- Programmed cell death protein 1 (PD-1)/PD-1 ligand (PD-L1) inhibitors show promise in cancer therapy.
- Cervical cancer (CC) exhibits low response rates to PD-1/PD-L1 inhibitors, linked to immunosuppressive tumor microenvironments (TME).
- Tumor-associated macrophages (TAMs) contribute to a suppressive TME and influence therapeutic outcomes.
Purpose of the Study:
- To elucidate the regulatory mechanisms of TAMs on PD-L1 expression in cervical cancer.
- To investigate the correlation between TAM infiltration and PD-L1 expression in CC patients.
- To explore the impact of TAMs on CC cell behavior and progression.
Main Methods:
- Immunohistochemistry to assess PD-L1, CD68, and CD163 expression in CC tissues.
- Bioinformatics analysis to identify macrophage subtypes involved in PD-L1 regulation.
- Co-culture models to evaluate TAM effects on CC cell morphology, migration, and invasion, and PD-L1 regulation.
Main Results:
- PD-L1 expression on tumor cells correlates with poor prognosis and CD163+ TAM infiltration.
- Bioinformatics analysis indicated associations between PD-L1 expression and M1/M2 TAM infiltration.
- Co-culture experiments revealed M1/M2 TAMs upregulate PD-L1, with M2 TAMs potentially acting via the PI3K/AKT pathway. TAMs also enhanced CC cell migration and invasion.
Conclusions:
- PD-L1 expression serves as a prognostic factor in CC, linked to CD163+ TAM infiltration.
- M2 TAMs upregulate PD-L1 expression in CC cells via the PI3K/AKT pathway, promoting tumor progression.
- TAMs influence CC cell migration, invasion, and overall tumor progression, suggesting therapeutic targeting potential.
More Related Videos
Related Concept Videos
02:23Abnormal Proliferation
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...
01:22PI3K/mTOR/AKT Signaling Pathway
01:19Interactions Between Signaling Pathways
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
01:31The Intrinsic Apoptotic Pathway