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Harnessing immune plasticity to develop new immune therapies for breast cancer

Project Member(s): Gallego Ortega, D.

Funding or Partner Organisation: National Breast Cancer Foundation (Investigator Initiated Research Scheme)
National Breast Cancer Foundation (Investigator Initiated Research Scheme)

Start year: 2022

Summary: Immunotherapies, especially T cell-centred approaches such as checkpoint inhibitors, have led to remarkable successes in treatment of advanced metastatic cancers. However, so far these approaches have only been effective in a small subset of breast cancer patients, highlighting a clear clinical need for improved immunotherapies to treat breast cancer and especially triple negative breast cancer (TNBC), where few treatment options are available to patients. We have developed an approach that modulates the function of innate immune cells, called neutrophils, in tumours. Applying microbial therapy switched neutrophil function in tumours from pro- to anti-cancer and directed neutrophil antimicrobia capabilities against tumour cells. Intravital two-photon microscopy showed that activated neutrophils directly removed tumour cells. We also found that sustained neutrophil activation is important for efficacy of microbial therapy. Notably, microbial treatment of breast cancer tumours efficiently inhibited tumour growth in pre-clinical TNBC models and substantially increased survival. This is significant since it shows that this therapeutic approach can work in breast tumours that are largely resistant to currently available immunotherapy. In this project we will build on these exciting results to develop and optimise our immunotherapeutic approach to translate it to the clinic. We will apply innovative genomic technologies (scRNAseq) together with intravital imaging to identify specific neutrophil functions that are important for their anti-tumour capabilities. We will determine optimal approaches for administering microbial therapy to activate neutrophils and maintain them in the anti-tumour state to achieve maximum therapeutic effect. Finally, we will investigate whether we can generate a memory immune response that can protect from subsequent tumour challenges and metastatic disease.

FOR Codes: Clinical health, Oncology and carcinogenesis, Immunology