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Background <p>Dendritic cell (DC) maturation is critical for antitumor immunity. Interferon-alpha 2b (IFNα2b) enhances dendritic cell function; however, its effects on monocyte-derived DCs (Mo-DCs) from NSCLC patients remain unclear. This in vitro experimental study investigates IFNα2b-mediated Mo-DC maturation and immune function in both healthy individuals and NSCLC patients.</p> Methods <p>Peripheral blood samples were collected from healthy donors (<i>n</i> = 30; 18–65 years; 17 males, 13 females) and newly diagnosed, untreated stage I NSCLC patients (<i>n</i> = 30; 18–65 years; 16 males, 14 females). PBMCs were isolated by density gradient centrifugation, and adherent monocytes were cultured with recombinant human GM-CSF and IL-4 for 3 days to generate immature Mo-DCs. Maturation was induced using IFN-α2b or LPS. Maturation markers, cytokine profiles, and immune cell activation were analyzed using flow cytometry and ELISA. Oxidative stress parameters and functional assays evaluating cytotoxic T lymphocyte (CTL)-mediated killing of NSCLC cells were also performed.</p> Results <p>IFNα2b-matured Mo-DCs exhibited significantly increased expression of maturation markers including CD1d, NFκB, STAT3, BATF3, PU.1, and DNAPKcs compared to untreated controls. Co-culture with peripheral blood mononuclear cells (PBMCs) resulted in enhanced NK cell activation (increased CD56 + expression) and promoted a pro-inflammatory Th1-skewed response, characterized by elevated secretion of IL-12, IFNγ, and TNF-α, while T<sub>H</sub>2- and T<sub>H</sub>17-associated cytokines (IL-4, IL-10, IL-17, IL-1β) were suppressed. Oxidative stress analysis revealed reduced reactive oxygen species (ROS) levels in IFNα2b-matured Mo-DCs with decreased glutathione (GSH) content and increased nitric oxide (NO) release. Importantly, IFNα2b-matured Mo-DCs significantly enhanced CTL-mediated killing of NSCLC cells (A549 line).</p> Conclusion <p>IFNα2b enchances dendritic cell maturation and promotes T<sub>H</sub>1-skewed anti-tumor immune responses, supporting its potential as an adjuvant to enhance DC-based immunotherapy in NSCLC patients.</p>

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Interferon-alpha 2b (IFNα2b) enhances monocyte-derived dendritic cell maturation and Th1-skewed anti-tumor immunity in non-small cell lung cancer

  • 期刊论文

  • 发表日期：

    2025年12月6日

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  • Soham Bindu,
  • Oishi Mukherjee,
  • Roshni Bibi,
  • Melvin George,
  • Koustav Sarkar

摘要

Background

Dendritic cell (DC) maturation is critical for antitumor immunity. Interferon-alpha 2b (IFNα2b) enhances dendritic cell function; however, its effects on monocyte-derived DCs (Mo-DCs) from NSCLC patients remain unclear. This in vitro experimental study investigates IFNα2b-mediated Mo-DC maturation and immune function in both healthy individuals and NSCLC patients.

Methods

Peripheral blood samples were collected from healthy donors (n = 30; 18–65 years; 17 males, 13 females) and newly diagnosed, untreated stage I NSCLC patients (n = 30; 18–65 years; 16 males, 14 females). PBMCs were isolated by density gradient centrifugation, and adherent monocytes were cultured with recombinant human GM-CSF and IL-4 for 3 days to generate immature Mo-DCs. Maturation was induced using IFN-α2b or LPS. Maturation markers, cytokine profiles, and immune cell activation were analyzed using flow cytometry and ELISA. Oxidative stress parameters and functional assays evaluating cytotoxic T lymphocyte (CTL)-mediated killing of NSCLC cells were also performed.

Results

IFNα2b-matured Mo-DCs exhibited significantly increased expression of maturation markers including CD1d, NFκB, STAT3, BATF3, PU.1, and DNAPKcs compared to untreated controls. Co-culture with peripheral blood mononuclear cells (PBMCs) resulted in enhanced NK cell activation (increased CD56 + expression) and promoted a pro-inflammatory Th1-skewed response, characterized by elevated secretion of IL-12, IFNγ, and TNF-α, while TH2- and TH17-associated cytokines (IL-4, IL-10, IL-17, IL-1β) were suppressed. Oxidative stress analysis revealed reduced reactive oxygen species (ROS) levels in IFNα2b-matured Mo-DCs with decreased glutathione (GSH) content and increased nitric oxide (NO) release. Importantly, IFNα2b-matured Mo-DCs significantly enhanced CTL-mediated killing of NSCLC cells (A549 line).

Conclusion

IFNα2b enchances dendritic cell maturation and promotes TH1-skewed anti-tumor immune responses, supporting its potential as an adjuvant to enhance DC-based immunotherapy in NSCLC patients.