Fig 1.
(A) Common strategies employed in chemotherapy and in adaptive therapy to deal with the proliferation of malignant cells. In adaptive therapy, treatment is used sparingly and in a temporally dynamic fashion, and this both increases the competitive advantage of chemo-sensitive cells and maintains a stable tumor burden. B) In a similar manner, when the immune system kills only some sensitive/visible tumor cells, it allows for maintenance of a stable tumor burden because this population competes with cells that are resistant to immune attack.
Fig 2.
Evolution of the trade-off between TSMs and the risk of AI with age and reproductive status.
During the reproductive period and before, NAT could result in a compromise between tumor suppression and the potential hazards to normal tissue to maintain cancer incidence at a low rate. This compromise could be extended in species in which there is grandparental care. After this reproductive period, NAT will decrease because tumor suppression costs will exceed the benefits, and tumor incidences will increase. Dashed lines are used for species without grandparental care and solid lines for species with grandparental care. AI, autoimmunity; NAT, natural adaptive therapy; TSM, tumor-suppressive mechanism.
Fig 3.
NAT hypothesis applied to the equilibrium phase of immunoediting.
If the immune system cannot fully eliminate cancer cells, it could adopt NAT to limit impact on fitness through an equilibrium phase. During this phase, the immune system could maintain a stable tumor burden to increase intratumor competition and therefore delay the apparition of immuno-resistant cells. CTL, cytotoxic T cells; DC, dendritic cells; NAT, natural adaptive therapy; TAM, tumor-associated macrophages; Treg, regulatory T lymphocytes.