Pre-clinical exercise oncology as a discovery engine: metabolic reprogramming, microbial rewiring, and myokine signaling (IMAGE)
Caption
In this schematic, pre-clinical mechanistic exercise work (top) is proposed to lead to novel translational advances beyond the treadmill (bottom). (a) Exercise increases circulating levels of specific metabolites, such as lactate, which has been shown to directly activate CD8 T cells, leading to tumor cell death [top]; these data suggest the possibility of serial injection of anti-tumor metabolites (exerkines) like L-lactate to reduce tumor growth [bottom]; (b) Exercise can remodel the phenotype of the gut microbiome, leading to a distinct metabolomic signature (increased microbial formate) that promotes CD8 T cell activation via NRF2, reduced tumor growth, and enhanced responses to cancer immunotherapy (ICI) in pre-clinical melanoma [top]; these data suggest the possibility of utilizing FMT from exercised to non-exercised hosts to promote similar ICI sensitivity and reduced tumor growth [bottom]; (c) Exercise promotes release of myokines (such as IL-6 and IL-15) from muscle, which can reprogram immune cell subsets (NK Cells and CD8 T Cells) and reduce tumor growth (in melanoma and PDAC, respectively) [top]; further data suggest the possibility of using an IL-15 superagonist agent to promote tumor cell death and improve survival in PDAC models, without the need for exercise [bottom]. Created in BioRender. Kurz, E. (2026) https://BioRender.com/0piec23. ICI: immune checkpoint inhibitor; FMT: fecal microbial transfer; CD8: cluster of differentiation 8; NRF2: nuclear factor erythroid 2-related factor 2; IL: interleukin; NK: natural killer; PDAC: pancreatic ductal adenocarcinoma.
Credit
© Emma S. Kurz, Dafna Bar-Sagi 2026.
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Credit must be given to the creator.
License
CC BY