Genetic instability as a driver for immune surveillance [article]

Guim Aguade, Ricard Sole
2019 bioRxiv   pre-print
Genetic instability is known to relate with carcinogenesis by providing tumors with a mechanism for fast adaptation. However, mounting evidence also indicates causal relation between genetic instability and improved cancer prognosis resulting from efficient immune response. Highly unstable tumors seem to accumulate mutational burdens that result in dynamical landscapes of neoantigen production, eventually inducing acute immune recognition. How are tumor instability and enhanced immune response
more » ... elated? An important step towards future developments involving combined therapies would benefit from unraveling this connection. In this paper we present a minimal mathematical model to describe the ecological interactions that couple tumor adaptation and immune recognition while making use of available clinical estimates of relevant parameters. The possible evolutionary trade-offs associated to both cancer replication and T cell response are analysed, indicating that cancer-clearance states become attainable when both mutational load and immune migration are enhanced. Furthermore, the model predicts the presence of well-defined transitions towards tumor control and eradication after increases in genetic instability consistent with available data of tumor control after Mismatch Repair knockout.
doi:10.1101/527689 fatcat:nnau5kr63jabfd5qzxm72ulj7m