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<p>Cell free DNA (cfDNA) is detectable at low concentrations in the plasma of healthy subjects and at high concentrations in disorders characterized by a high rate of necrotic events, such as tumors and vasculitis, leading to the release of necrotic DNA into the surrounding tissue and the bloodstream. Although cfDNA may act as a danger signal by binding to DNA sensors, triggering inflammation and immune responses, elevated cfDNA concentrations instead may exert immunoregulatory activities. Here, we show that exogenously administered cfDNA mediates immunoregulatory functions in vivo, in particular, it protects lupus-prone mice from disease progression and favors tumor growth in tumor-challenged mice. Our data suggest that cfDNA mediates immune regulatory activities by directly interacting with MHC class II molecules on antigen-presenting cells and through recruitment of regulatory T cells. This study unveils unprecedented biologic functions of cfDNA with significant pathogenic relevance and remarkable implications for the treatment of cancer patients.</p>

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Immunoregulatory properties of cell free DNA

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年8月26日

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  • Francesca Ferrera,
  • Tiziana Altosole,
  • Samuele Tardito,
  • Giuseppina Astone,
  • Cinzia Bernardi,
  • Alessia Parodi,
  • Chiara Marini,
  • Giuseppina Conteduca,
  • Elena Cichero,
  • Annalisa Salis,
  • Leonardo Arpesella,
  • Laura Camporesi,
  • Andrea Lagazio,
  • Valentina Rigo,
  • Andrea Pigozzo,
  • Gianluca Damonte,
  • Paola Fossa,
  • Daniela Fenoglio,
  • Raffaele De Palma,
  • Giorgio Inghirami,
  • Gilberto Filaci

摘要

Cell free DNA (cfDNA) is detectable at low concentrations in the plasma of healthy subjects and at high concentrations in disorders characterized by a high rate of necrotic events, such as tumors and vasculitis, leading to the release of necrotic DNA into the surrounding tissue and the bloodstream. Although cfDNA may act as a danger signal by binding to DNA sensors, triggering inflammation and immune responses, elevated cfDNA concentrations instead may exert immunoregulatory activities. Here, we show that exogenously administered cfDNA mediates immunoregulatory functions in vivo, in particular, it protects lupus-prone mice from disease progression and favors tumor growth in tumor-challenged mice. Our data suggest that cfDNA mediates immune regulatory activities by directly interacting with MHC class II molecules on antigen-presenting cells and through recruitment of regulatory T cells. This study unveils unprecedented biologic functions of cfDNA with significant pathogenic relevance and remarkable implications for the treatment of cancer patients.