Table 2.
Summary of key mechanisms of therapeutic synergy between localised therapy combinations and ICPI.
| Therapy-induced mechanisms | Immunogenic effects promoting synergy with ICPI | References |
|---|---|---|
| Nucleic acid sensing | Induced IFN type I signalling | (19–23) |
| cGAS/STING activation | → T cell recruitment | |
| RIG-I/MAVS activation | → Augmented CD8 T cell cytotoxicity | |
| → Increased DC cross-priming | ||
| DAMP release/exposure | (24–26) | |
| ATP | Recruitment and activation of DCs | |
| HMGB1 | Increased phagocytosis | |
| CALR | Production of pro-inflammatory cytokines | |
| Neo-antigen expression and processing | Increased peptide pool | (27–31) |
| Increased diversity of TCR repertoire | ||
| Generation of tumour specific T cells | ||
| MHC class I upregulation | Augmented CD8 T cell priming | (27) |
| Enhanced tumour cell killing | ||
| Death-receptor upregulation | Augmented NK cell and CD8 T cell cytotoxicity | (32, 33) |