Evaluating the potential for maximized T cell redistribution entropy to improve abscopal responses to radiotherapy

The potential for local radiation therapy to elicit systemic (abscopal) anti-tumor immune responses has been receiving a significant amount of attention over the last decade. We recently developed a mathematical framework designed to simulate the systemic dissemination of activated T cells among multiple metastatic sites. This framework allowed the identification of non-intuitive patterns of T cell redistribution after localized therapy, and offered suggestions as to the optimal site to irradiate in order to maximize T cell redistribution entropy. Here, we evaluate the potential for this optimized T cell redistribution to increase the magnitude of an immune-mediated abscopal response, and describe the approach that would be necessary to validate this in the clinical setting. Primary challenges include the quantification of microenvironmental conditions at each site and evaluation of their influence on local T cell extravasation and expansion, efficient segmentation and delineation of multiple tumor sites on PET/CT scans, and thorough validation of model prediction performance.