Early detection of recurrence by using specific biomarkers is still a clinically unmet need although methodologies for monitoring tumor markers, cell-free DNA and circulating tumor cells have been established for decades. Because recurrence is developed from metastatic or dormant cancer cells that are under immune surveillance, alteration in the population and function of immune cells may promote recurrence. In this study, we utilized an animal model to imitate breast tumor recurrence after surgical resection and investigated the abundance and gene expression profile of immune cells by using two NanoString Panels. Our results showed that myeloid-derived-suppressor cells (MDSC) were significantly increased during recurrence. Comparison of our NanoString data with a single-cell RNA sequencing dataset of MDSC in another spontaneous breast cancer model identified colony-stimulating factor 3 receptor (Csf3r)-positive MDSC as a potential marker to predict tumor recurrence. In vitro experiments demonstrated that Csf3R+ MDSC exhibited enhanced ROS levels and stronger T cell suppression ability. Furthermore, these findings were validated in two published PBMC databases. Overall design: An orthotopic model by inoculating luciferase-tagged mouse 4T1 (4T1-luci) breast cancer cells into the 4th mammary fat pad of BALB/c mice was established to study the alteration of immune cell populations in blood during tumor recurrence. At 3 weeks after inoculation, paired normal and tumor-bearing mice were euthanized for blood collection and mononuclear cell isolation. Tumors of another 3 tumor-bearing mice were removed by surgical resection and tumor recurrence was monitored by detecting the presence of bioluminescence using an IVIS imaging system. When a bioluminescent signal appeared, the mouse was euthanized for blood collection. Tumor recurrence in the mice was variable and was detected around 2-4 weeks after tumor dissection (thus weeks 5 to 7 after cancer cell inoculation). PBMC were spun down by centrifugation at 1500 rpm for 10 min at 4℃ and washed twice with phosphate-buffered saline (PBS) and RNA was isolated by using Direct-Zol RNA Miniprep Kits (ZYMO RESEARCH). Isolated mononuclear cells were subjected to NanoString analysis using nCounter Mouse Myeloid Innate Immunity V2 panel (754 genes) and Mouse PanCancer Immune Profiling Panel (770 genes).