Figure 1: Representative results from the three models. Top left: A game-theoretic model uses trajectories (blue) through the expression space of CCR7 and PD-L1 under AI therapy to predict cumulative metastatic potential (red gradient). Top right: A cellular automaton model examines the possible mechanisms for inducing CCR7 expression, comparing spatial heterogeneity patterns with those seen in biopsies. Bottom: An ODE model predicts the improvement in PEPI score following combination AI and CI therapy.Abstract-Based on clinical data from hormone positive breast cancer patients, we determined that there is a potential tradeoff between reducing tumor burden and altering metastatic potential when administering combination therapy of aromatase inhibitors and immune checkpoint inhibitors. While hormone-deprivation therapies serve to reduce tumor size in the neoadjuvant setting pre-surgery, they may induce tumors to change expression patterns towards a metastatic phenotype. We used mathematical modeling to explore how the timing of the therapies affects tumor burden and metastatic potential with an eye toward developing a dynamic prognostic score and reducing both tumor size and risk of metastasis.

The immune system is increasingly being recognized for its untapped potential in being recruited to attack tumors in cancer therapy. The main challenge, however, is that most tumors exist in a state of immune tolerance where the patient's immune system has become insensitive to the cancer cells. In order to investigate the ability to use chemotherapy to break immune tolerance, we created a mathematical modeling framework for tumor-immune dynamics. Our results suggest that optimal chemotherapy scheduling must balance two opposing objectives: maximal tumor reduction and preserving patient immune function. Successful treatment requires therapy to operate in a "Goldilocks Window" where patient immune health is not overly compromised. By keeping therapy "just right", we show that the synergistic effects of immune activation and chemotherapy can maximize tumor reduction and control.