Dynamic Phenotyping Reveals Highly Personalized, Integrated Host-Tumor Crosstalk During Exercise in Cancer Patients

How exercise therapy modulates the host systemic environment to regulate tumor evolution in humans is not known. We performed personalized, multiparametric, longitudinal profiling before, during, and after short-term endurance exercise in 13 patients with solid tumors in a preoperative “window” study. Time-series analyses revealed hundreds of host molecular changes in the plasma metabolome and proteome and gut microbiome involved in a diverse-array of biological processes. Host systemic environmental changes were paralleled by modulation of core tumor gene expression pathways notably tumor cell cycle regulation, stress response, and metabolism. Integrative network analyses revealed the complexity of the host – tumor interaction under exercise regulation, elucidating novel mechanistic insights. Variability at baseline and during intervention highlighted highly personalized responses to uniform exercise therapy. Our study provides an example of how generation of a longitudinal high-definition dataset provides a framework for interrogation of the integrative, host-tissue response to exercise in clinical populations