PT  - JOURNAL ARTICLE
AU  - Josua Aponte Serrano
AU  - Amit Hagar
TI  - Run for your life – an integrated virtual tissue platform for incorporating exercise oncology into immunotherapy
AID  - 10.1101/2020.09.04.283416
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.09.04.283416
4099  - http://biorxiv.org/content/early/2020/10/16/2020.09.04.283416.short
4100  - http://biorxiv.org/content/early/2020/10/16/2020.09.04.283416.full
AB  - The purpose of this paper is to introduce a novel in silico platform for simulating early stage solid tumor growth and anti-tumor immune response. We present the model, test the sensitivity and robustness of its parameters, and calibrate it with clinical data from exercise oncology experiments which offer a natural biological backdrop for modulation of anti-tumor immune response. We then perform two virtual experiments with the model that demonstrate its usefulness in guiding pre-clinical and clinical studies of immunotherapy. The first virtual experiment describes the intricate dynamics in the tumor microenvironment between the tumor and the infiltrating immune cells. Such dynamics is difficult to probe during a pre-clinical study as it requires significant redundancy in lab animals and is prohibitively time-consuming and labor-intensive. The result is a series of spatiotemporal snapshots of the tumor and its microenvironment that can serve as a platform to test mechanistic hypotheses on the role and dynamics of different immune cells in anti-tumor immune response. The second virtual experiment shows how dosage and/or frequency of immunotherapy drugs can be optimized based on the aerobic fitness of the patient, so that possible adverse side effects of the treatment can be minimized.Competing Interest StatementAH is the inventor and owner of US patent 10.497.467.B2 Systems and Methods for Optimizing Diagnostics and Therapeutics with Metabolic ProfilingCC3DCompuCell 3DCETchronic endurance trainingCPMcellular Potts modelCTLcytotoxic T lymphocytesHIIThigh intensity interval trainingICIimmune checkpoint inhibitorsMCSMonte Carlo stepsTMEtumor microenvironment