The host STING pathway at the interface of cancer and immunity

Area of Science:

• Immunology
• Oncology
• Molecular Biology

Background:

• Many human cancers exhibit spontaneous adaptive immunity, evidenced by tumor-infiltrating CD8+ T cells.
• The innate immune pathways responsible for detecting cancer and initiating antitumor responses remain incompletely understood.
• Type I interferons (IFNs) play a critical role in natural adaptive antitumor immunity.

Purpose of the Study:

• To identify the innate immune sensing pathway responsible for detecting cancer and inducing adaptive antitumor immunity.
• To investigate the role of the STING pathway in sensing tumor-derived DNA and initiating type I IFN production.
• To evaluate the therapeutic potential of STING pathway activation in cancer treatment.

Main Methods:

• Analysis of innate immune sensing pathways in the context of spontaneous antitumor immunity.
• Investigating the sensing of cytosolic tumor-derived DNA by dendritic cells (DCs).
• Correlating STING pathway activation with IFN-β production and T cell responses.

Main Results:

• The stimulator of IFN genes (STING) pathway was identified as a key sensor of cytosolic tumor-derived DNA in tumor-infiltrating DCs.
• STING pathway activation correlates with increased IFN-β production.
• Activation of the STING pathway leads to the induction of antitumor T cells.
• Intratumoral administration of STING agonists demonstrated significant therapeutic efficacy in preclinical mouse models.

Conclusions:

• The STING pathway is a critical innate immune sensor for detecting cancer and initiating adaptive antitumor responses.
• STING agonists represent a promising therapeutic strategy for augmenting antitumor immunity.
• STING agonists are advancing into clinical trials for cancer therapy.