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Extrinsic Phagocyte-Dependent STING Signaling Dictates the Immunogenicity of Dying Cells

Jeonghyun Ahn1, Tianli Xia1, Ailem Rabasa Capote1

  • 1Department of Cell Biology, The University of Miami Miller School of Medicine, University of Miami, 511 Papanicolaou Building, 1550 NW 10th Avenue, Miami, FL 33136, USA.

Cancer Cell
|May 1, 2018
PubMed

Insights

Dying cells activate antigen-presenting cells (APCs) through STING signaling when containing cytosolic DNA or cyclic di-nucleotides (CDNs). This mechanism promotes anti-tumor immunity and avoids harmful inflammation, offering a cancer treatment strategy.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cancer Research

Background:

  • Antigen-presenting cells (APCs) activation by dying cells is tightly regulated to prevent excessive inflammation.
  • Uncontrolled inflammation can lead to autoimmune diseases, while insufficient immune responses impair anti-tumor activity.

Purpose of the Study:

  • To elucidate the molecular mechanisms by which dying cells stimulate APCs for effective anti-tumor immunity.
  • To identify the role of cytosolic DNA and cyclic di-nucleotides (CDNs) in APC activation.
  • To explore the STING (stimulator of interferon genes) pathway's involvement in this process.

Main Methods:

  • Investigated the role of cytosolic double-stranded DNA and CDNs in stimulating APCs.
  • Utilized STING signaling pathway agonists and antagonists.
  • Assessed the impact of these factors on antigen cross-presentation by APCs.

Main Results:

  • Engulfed cells with cytosolic DNA or CDNs activate APCs via extrinsic STING signaling.
  • STING agonists are essential for dying cells to stimulate APCs in trans.
  • Cytosolic STING activators act as danger-associated molecular patterns (DAMPs) during viral infection or DNA damage.

Conclusions:

  • Cytosolic STING activators are key mediators linking dying cells to APC stimulation and anti-tumor immunity.
  • This pathway promotes immunogenic tumor cell death and adaptive immune responses.
  • Understanding this mechanism offers a potential therapeutic strategy for cancer treatment by enhancing anti-tumor immunity.
Keywords:
STINGSTING-dependent adjuvants (STAVs)anti-tumor T cellsantigen-presenting cells (APCs)cyclic di-nucleotides (CDNs)innate immunityinterferon

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