Immunoediting
Immunoediting is the process by which the immune system shapes tumor development in three phases: elimination, equilibrium, and escape. Robert Schreiber and colleagues formulated the model in 2004, building on the immune surveillance hypothesis of Burnet and Thomas.
The three phases
- Elimination. Immune cells — cytotoxic T cells, natural killer cells, macrophages — detect and destroy a transformed cell population outright. The tumor never becomes clinically visible.
- Equilibrium. Variant cells that resist killing persist under continuous immune pressure. They divide slowly and acquire further mutations, held in a dynamic stalemate that can last years. This is the phase in which the immune system acts as a selective force: it decides which variants survive.
- Escape. A variant the immune system can no longer restrain expands into clinical disease.
Escape mechanisms
Tumors reach escape through several routes: loss or down-regulation of HLA-A so antigens go undisplayed, expression of PD-L1 to disable attacking T cells, secretion of TGF-β and other suppressive factors, recruitment of regulatory immune cells, and selection for antigen-loss variants under immune pressure. Each escape phenotype is evidence that equilibrium was real — the tumor evolved under attack.
Therapeutic implications
Checkpoint inhibitors (CTLA-4, PD-1) work by releasing the brakes the tumor has placed on immune cells, which is only possible when the immune attack still exists to be released. Response correlates with pre-existing T-cell infiltration, high mutation load (more visible antigens), and preserved antigen display.
Notes
- Draft stub - maintenance agent to expand with the Dunn/Schreiber 2004 paper, the methylcholanthrene sarcoma mouse experiments, and the equilibrium-phase evidence.