Radiotherapy Combined with Novel STING-Targeting Oligonucleotides Results in Regression of Established Tumors

Area of Science:

• Immunology
• Oncology
• Radiotherapy

Background:

• Cytotoxic therapies release tumor antigens but face an immunosuppressed tumor microenvironment.
• STING (stimulator of interferon genes) activation by cyclic dinucleotides induces inflammatory pathways in tumors.

Purpose of the Study:

• To investigate the adjuvant potential of STING ligands combined with radiotherapy for pancreatic cancer treatment.
• To explore the mechanisms underlying the synergistic effects of STING activation and radiotherapy.

Main Methods:

• Utilized a murine model of pancreatic cancer.
• Administered CT-guided radiotherapy combined with a novel STING ligand.
• Performed mechanistic investigations including immune cell profiling and cytokine analysis.
• Assessed STING expression in human pancreatic tumors.

Main Results:

• The combination therapy synergistically controlled local and distant tumors in a murine model.
• Early-stage tumor control involved T-cell-independent, TNFα-dependent hemorrhagic necrosis.
• Later-stage disease control was mediated by CD8 T-cells.
• STING was widely expressed in human pancreatic tumors and stromal cells.

Conclusions:

• STING ligand and radiotherapy combination demonstrates potent synergistic anti-tumor activity.
• This combination therapy leverages both innate and adaptive immune responses for cancer control.
• The findings support the development of STING ligands as a novel adjuvant for pancreatic cancer radiotherapy.