Knowledge of the significance of the immune response and the promise of immunotherapy in the treatment of non-resectable tumors is rapidly becoming widespread and has largely become so already in the medical and scientific communities. The critical importance of evolution in disease progression is similarly ubiquitously understood, though awareness of this is much less novel. Accordingly, the first goal of this project is to establish an integrative understanding of the dynamics of these two processes and, in particular, of the evolution of their interactions. The second goal is to investigate and develop new methods for maintaining optimal control in analogous rapidly evolving systems, with a focus on altering the immunological environment to guide the evolution of tumor cell populations toward subspaces of phenotypic distributions in which they can be stably maintained.