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Potential interactions between STING pathway and the complement system in immune regulation

BingXiao Zhang1, Yu Chen1, ChenGuang Wang2

  • 1Chinese Medicine Research Institute, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

Expert Review of Clinical Immunology
|June 18, 2025
PubMed
Abstract

Insights

The complement system and cGAS-STING pathway are key in immunity and cancer. Their complex interplay influences immune responses and disease, offering therapeutic targets for oncology and autoimmune disorders.

Area of Science:

  • Immunology
  • Molecular Biology
  • Oncology

Background:

  • The complement system and cGAS-STING pathway are critical innate immune components.
  • Both pathways are involved in pathogen defense and immune response modulation.
  • Their roles in cancer are complex, influencing tumor dynamics and immune cell activity.

Purpose of the Study:

  • To review the functions of the complement system and cGAS-STING pathway.
  • To explore the intricate interplay between these pathways.
  • To discuss their implications for disease pathogenesis, particularly in oncology.

Main Methods:

  • Literature review of studies published between 1983 and 2024.
  • Analysis of the roles of complement and cGAS-STING in pathogen clearance and tumor development.
  • Examination of the crosstalk and regulatory mechanisms between the two pathways.

Main Results:

  • Complement influences myeloid cells and T cell activities in cancer.
  • Intracellular complement (complosome) impacts cellular metabolism and autophagy.
  • STING activation affects tumor progression via NF-κB signaling, with context-dependent effects.
  • Potential regulatory crosstalk exists between complement and cGAS-STING pathways.

Conclusions:

  • Understanding the interplay between complement and cGAS-STING is crucial for elucidating disease pathogenesis.
  • Insights can guide the development of novel therapeutic strategies for immune modulation in cancer and autoimmune diseases.
  • Further investigation is warranted to fully unravel the complex roles of these pathways in health and disease.
Keywords:
ComplementNF-κBNLRP3cGAS-STINGinnate immunity

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