Profiling the immune landscape of breast cancer and the identification of potential therapeutic strategies

High perinuclear STING expression was associated with improved outcome in high-risk ER+ BC, treated with chemotherapy, suggesting a proportion of patients may benefit STING activation. However, successful systemic activation of STING has been difficult to date, as the natural ligand, cGAMP is rapidly degraded in the bloodstream. Therefore, a novel delivery system, capable of delivering cGAMP to the target tumour site is required.

Using the RALA peptide based delivery system, two novel methods to potentially activate STING signaling have been proposed with the unique advantage of suitability for in vivo application and translatability. The preliminary data presented in this study warrants further assessment of RALA/siRNA and RALA/cGAMP nanoparticles in a syngeneic model. <br><br> To conclude, a population of BC patients with low levels of STING activity and who do not benefit from current standard of care treatments have been identified.

These patients may benefit from STING activation however, given the upregulation of immune checkpoints, combination treatment with immune checkpoint inhibitors may be required. <br><br><i>Thesis embargoed until 31 July 2029.</i>