Necroptosis in both tumour and stromal compartments determines responsiveness to immunogenic cell death-based immunotherapy - PubMed
4 days ago
- #Necroptosis
- #Triple-negative breast cancer
- #Immunotherapy
- Necroptosis in both tumour and stromal compartments is crucial for responsiveness to immunogenic cell death (ICD)-based immunotherapy.
- A Brca1−/−p53−/− organoid-derived TNBC model shows RIPK1-driven ICD synergizes with anti-PD-1 therapy, leading to durable tumour control and immune memory.
- Both tumour-intrinsic and stromal necroptosis are required for therapeutic efficacy; deletion of Ripk1 or Mlkl in tumour cells or Mlkl in stroma impairs results.
- Immunologically 'cold' tumours can become responsive to ICD-based therapy with STING agonists.
- IAP antagonism with checkpoint blockade depends on coordinated necroptosis in tumour and stromal cells, highlighting the importance of tumour microenvironment in ICD-targeted immunotherapies.