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Isolation of Murine Lymph Node Stromal Cells
Published on: August 19, 2014
Circulating innate lymphoid cells are dysregulated in patients with prostate cancer
Daniela Claudia Maresca1, Evelina La Civita2, Benedetta Romano1
1Department of Pharmacy, School of Medicine, University of Naples Federico II, 80138, Naples, Italy.
Background:
Prostate cancer (PCa) is the second most common cancer affecting men globally, especially those aged 50 years and above. Despite substantial progress in terms of both prognosis and therapy, PCa remains a significant health concern, necessitating the identification of novel therapeutic targets. Innate lymphoid cells (ILCs) have emerged as critical modulators of tumor immunity, exhibiting both pro- and antitumoral effects. However, little is known yet about their contribution in PCa. This study investigated the phenotypic and functional profiles of ILC subsets in the peripheral blood mononuclear cells (PBMCs) of patients with PCa stratified by Gleason score.
Methods:
PBMCs were isolated by Lymphoprep. ILC frequency and activity were evaluated by flow cytometry. The levels of ILC-activating cytokines were analyzed by multiplex assay in the serum of healthy donors (HDs) and patients with PCa. To evaluate the crosstalk between ILC2s and cancer cells, PC3 and DU145 human PCa cell lines were used.
Results:
We found a stage-dependent increase in the protumoral ILC2 frequency and a concurrent decrease in antitumoral ILC1s in patients with PCa compared with healthy controls. Interestingly, the frequency of ILC2s was higher in patients with elevated prostate-specific antigen (PSA) values, suggesting their potential as molecular predictor for defining the risk category of patients with PCa at diagnosis. Importantly, patients with PCa exhibited hyperactivated ILC2s, characterized by elevated interleukin (IL)-13 and IL-5 production, while ILC1s displayed reduced tumor necrosis factor (TNF)-α and interferon (IFN)-γ secretion. Furthermore, serum levels of ILC2-activating cytokines IL-33, IL-18, and prostaglandin D2 (PGD2) were elevated in patients with PCa. In vitro co-culture experiments demonstrated that PCa cell lines, capable of secreting these cytokines, could directly enhance ILC2 activity. Likewise, ILC2-derived IL-13 promoted PCa cell migration and invasion.
Conclusions:
Collectively, our findings highlight a dysregulated ILC profile in PCa, characterized by ILC2 dominance and heightened activity at the expense of ILC1s, suggesting both ILC1s and ILC2s as potential therapeutic targets for PCa treatment.
Insights
Prostate cancer (PCa) shows increased protumoral innate lymphoid cells (ILC2s) and decreased antitumoral ILC1s. These ILC subsets are potential therapeutic targets for PCa treatment.
Area of Science:
- Immunology
- Oncology
Background:
- Prostate cancer (PCa) is a significant global health concern, especially for men over 50.
- Novel therapeutic targets are needed despite advances in PCa prognosis and therapy.
- Innate lymphoid cells (ILCs) modulate tumor immunity, but their role in PCa is unclear.
Purpose of the Study:
- Investigate the phenotypic and functional profiles of ILC subsets in PCa patients.
- Determine the contribution of ILCs to PCa immunity and progression.
- Stratify ILC profiles based on Gleason score and prostate-specific antigen (PSA) levels.
Main Methods:
- Isolated peripheral blood mononuclear cells (PBMCs) from PCa patients and healthy donors.
- Evaluated ILC frequency and activity using flow cytometry.
- Analyzed serum cytokine levels and performed in vitro co-culture experiments with PCa cell lines.
Main Results:
- Increased ILC2 frequency and decreased ILC1 frequency observed in PCa patients.
- Elevated ILC2 frequency correlated with higher PSA values.
- Hyperactivated ILC2s produced IL-13 and IL-5; ILC1s showed reduced TNF-α and IFN-γ secretion.
- Elevated serum levels of ILC2-activating cytokines (IL-33, IL-18, PGD2) found in PCa patients.
- PCa cell lines enhanced ILC2 activity, and IL-13 from ILC2s promoted PCa cell migration and invasion.
Conclusions:
- PCa is characterized by a dysregulated ILC profile with ILC2 dominance and heightened activity.
- Reduced ILC1 function and increased ILC2 activity contribute to PCa progression.
- Both ILC1s and ILC2s represent potential therapeutic targets for PCa treatment.
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