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Interferon signaling and STING pathway in head and neck cancers: unlocking immune secrets and therapeutic frontiers

Kosar Zolfaghari1, Mohammad Yazdi1,2, Shaghayegh Mohammadioun1

  • 1Cancer Immunology Project (CIP), Universal Scientific Education and Research Network (USERN), Tehran, Iran.

Cancer Cell International
|October 4, 2025
PubMed

Insights

Interferons (IFNs) and STING pathway signaling play crucial roles in head and neck squamous cell carcinomas (HNSCCs). Understanding their dual roles in immunity and cancer progression is key for effective treatment strategies.

Area of Science:

  • Immunology
  • Oncology
  • Molecular Biology

Background:

  • Head and neck squamous cell carcinomas (HNSCCs) are a significant global health concern.
  • Immune responses critically influence cancer progression and patient outcomes.
  • Interferons (IFNs) are vital innate immune components modulating the tumor microenvironment (TME) and cancer cell fate.

Purpose of the Study:

  • To review Interferon (IFN) signaling, with a specific focus on the cGAS-stimulator of interferon genes (STING) pathway.
  • To discuss the role of STING signaling in modulating immunotherapy and chemotherapy efficacy in HNSCC.
  • To highlight the dual role of STING in tumor resistance and antitumor immunity.

Main Methods:

  • Literature review of Interferon (IFN) signaling pathways.
  • Focus on the cGAS-STING pathway's mechanism in cancer.
  • Analysis of STING's role in modulating therapeutic responses in HNSCC.

Main Results:

  • STING signaling identifies cytosolic DNA and initiates immune responses.
  • Aberrant cGAS-STING activation can lead to excessive type-I IFN release and tissue imbalance.
  • STING signaling exhibits a dual role, potentially promoting both tumor resistance and antitumor immunity.

Conclusions:

  • IFNs and the STING pathway are critical in HNSCC pathogenesis and immune modulation.
  • STING agonists show therapeutic potential but require careful toxicity management.
  • Further understanding of STING's role can optimize immunotherapy and chemotherapy for HNSCC.
Keywords:
Cancer immunologyHead and neck squamous cell carcinoma (HNSCC)InterferonSTING pathway

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