Purpose/Objective(s):
We previously introduced the immune temperature (
IT), a novel metric that quantifies tumors on a continuum (0-100°) beyond the traditional hot or cold classifications. Though prognostic, this formulation did not capture temporal dynamics or treatment-driven transitions, which we have now addressed in a modified
IT.
Materials/Methods:
Tumor-immune interactions are complex, dynamic, nonlinear, and multiscale. Therefore, we formulated an ordinary differential equation (ODE) system describing these interactions and generated regions of tumor progression and control separated by a boundary (separatrix) on the IT map. We then included radiotherapy (RT) in the ODE and investigated how different doses and schedules shift the separatrix. Using a cohort of 59 lung cancer patients who received post-surgery RT, we investigated whether RT regimes that drive patient trajectories toward high IT regions correspond to true locoregional control (LRC), and whether trajectories that remain trapped in low IT domains correspond to true locoregional failure, to determine accurate RT courses that steer the patient trajectories towards tumor control. To incorporate spatial and temporal heterogeneity, we developed a hybrid agent-based model (ABM) with a staggered lattice that simulates dynamic IT within a spatial tumor microenvironment. We also incorporated histopathological features to anchor the dynamic IT to tissue-level immune architecture.
Results:
We found: 1) RT regimes that steer lung cancer patient trajectories towards tumor control, 2) that RT shifts the separatrix in the IT map thus altering the probability of transition between RT-on and RT-off states, 3) the ABM recapitulates spatially resolved dynamic IT and agrees with RT response modelled trajectories, and 4) incorporating histopathological features may improve the predictive capacity of the IT.
Conclusion:
We reintroduce IT as a dynamic, spatially resolved metric that is a pan-cancer predictor of RT response and can guide clinical decisions toward accurate patient-specific precision medicine.
