Modeling and simulation of genotypic Tumor Mutational Burden and Phenotypic Immunogenicity biomarkers in cancer immunoediting with Ising-Hamiltonian characterization

The presented model, formed by relatively simple agents, generates emergent behaviors through which the phases of CI are identified. The flexible choice of control parameters is robust enough and provides a plausible explanation for the mechanisms through which tumors with high TMB and high immunogenicity (i.e., hot tumors) exhibit a higher probability of responding to immunotherapy treatment. Characterization via the Ising-model Hamiltonian supports this explanation by summarizing the system's dynamics, which, in turn, facilitates its analysis and methodical improvements. The complex interplay of TMB, TIP, and individual physiology is finely captured.