Brinedew

Unpublished draft

Immune Surveillance

Immune surveillance is the monitoring of the body’s tissues by immune cells that recognize and destroy transformed cells before they become tumors.

The hypothesis

Macfarlane Burnet and Lewis Thomas proposed in the 1950s and 1960s that the immune system’s function includes policing newly transformed cells. Long-lived organisms face a large cumulative risk of somatic cells acquiring oncogenic mutations, and cytotoxic T cells and natural killer cells recognize surface changes — viral antigens, stress ligands, reduced major histocompatibility complex display — that mark a transformed cell for killing.

Evidence and immunoediting

The clearest support comes from immunosuppression: transplant patients on long-term immunosuppressive drugs develop certain cancers, particularly virus-associated ones, at several times the normal rate. Mice lacking cytotoxic lymphocytes develop more spontaneous and carcinogen-induced tumors.

Work by Robert Schreiber and colleagues refined the hypothesis into the cancer immunoediting model, a three-phase sequence:

  1. Elimination — the immune system destroys a transformed cell population outright.
  2. Equilibrium — variant cells that resist killing persist under continuous immune pressure, dividing slowly and acquiring further mutations for years.
  3. Escape — a variant that the immune system can no longer restrain expands into clinical disease.

Equilibrium is the phase that makes surveillance a selective force: the immune system shapes which tumors eventually emerge. Tumors that escape do so through PD-L1 expression, antigen loss, and recruitment of regulatory T cells, which is why checkpoint inhibitors work by releasing the brake the tumor has placed on immune attack.

Open question: surveillance versus autoimmunity

How surveillance changes with age is an open problem for the governance synthesis. The anti-defector reading of inflammaging holds that immune activation escalates with cheater cell load - a time-independent policing policy acting on a rising input. At the same time, aged tissue clears senescent cells poorly, and senescent cells themselves resist apoptosis. One candidate antagonism that could account for both patterns without invoking wear: surveillance stringency trades off against autoimmunity. A more aggressive policing policy removes more damaged cells and attacks more borderline-self tissue; the autoimmunity cost of that policy rises as the tissue accumulates mutated, stressed, and borderline cells. Deriving the observed age changes in immune behavior from this trade-off - rather than from decay - is unfinished work in this synthesis.