HPB
Amblessed Onuma, MD MS
Resident
The Ohio State University Wexner Medical Center
Columbus, Ohio, United States
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Preoperative exercise therapy (PET) has been associated with reduced postoperative complications. The mechanism by which it can reduce liver metastases as well as confer organ protection following surgical stress is unknown. We hypothesize that PET can alter the hepatic immune microenvironment to allow the reduction of liver metastases from ischemic liver injury.
Methods:
Mice were randomly divided into PET and sedentary groups before tumor injection via the portal vein. The mice were subjected to surgical stress through a nonlethal model of segmental hepatic warm ischemia and reperfusion. To investigate how PET alters the hepatic immune microenvironment, single-cell RNA sequencing was performed on isolated hepatic non-parenchymal cells (CD45+) obtained from both groups.
Results:
Mice subjected to four weeks of PET showed a significant decrease in the number of gross metastases compared to sedentary mice after liver I/R. Single-cell RNA analysis of the hepatic immune cells revealed distinct macrophage and neutrophil subpopulations that correlated with cells derived from either PET or sedentary group. Among the macrophages, the expression of genes related to anti-tumor (CD169 and CD38) were significantly higher in PET mice compared to sedentary mice, whereas pro-tumor related genes CD163, MSR1, and MRC1 were significantly lower suggesting that exercise modulates the transcriptomic change in macrophages towards an anti-tumor phenotype.
Conclusions:
Our study is one of the first to show that preoperative exercise alters the hepatic immune microenvironment by shifting macrophages to a tumoricidal phenotype. This work offers a rationale for preoperative exercise therapy for cancer patients undergoing liver surgery thereby decreasing post-operative metastases and morbidity.