Peripheral myeloid-derived suppressor cell as a biomarker for diagnosing and predicting the treatment efficacy of colorectal cancer.

Abstract

e15535 Background: Colorectal cancer (CRC) is one of the most common malignant tumors in the world. The myeloid-derived suppressor cells (MDSCs) are major immunosuppressive cells in tumor microenvironment (TME). However, the diagnostic value of peripheral MDSCs of CRC patients and their treatment-related clinical significance are still ambiguous. Methods: Blood samples and clinical information were collected from 210 CRC patients and 102 healthy individuals. The frequencies of MDSCs were detected by flow cytometry. Immune-related cytokines were detected by Cytometric Beads Array. Paired blood samples before and after treatment were collected from another 175 CRC patients to assess the effect of therapeutic regimens on MDSCs. Results: Compared with healthy individuals, the proportions of total MDSCs (1.34 vs. 9.20, p < 0.0001), monocyte-MDSCs (Mo-MDSCs) (0.13 vs. 0.60, p < 0.0001) and polymorphonuclear-MDSCs (PMN-MDSCs) (0.87 vs. 7.32, p < 0.0001) were significantly increased in peripheral blood, while early-MDSCs (eMDSCs) were decreased (0.02 vs. 0.01, p < 0.0001). The sensitivity, specificity, and AUC of total MDSCs for CRC diagnosis were 80.5%, 90.2% and 0.9. The sensitivity, specificity, and AUC of total MDSCs combined with CEA were 89.5%, 89.0%, and 0.94, respectively. Correlation analysis showed that peripheral MDSCs were significantly correlated with leukocytes (r = 0.24~0.37), immune-related cytokines [especially IL-2 (r = 0.25~0.27), IL-5 (r = 0.26), IL-6 (r = 0.22~0.44), IL-8 (r = 0.18~0.32)], and biomarkers of gastrointestinal tumors (r = 0.24~0.41). Additionally, first-line chemotherapy FOLFOX and XELOX, or chemotherapy plus targeted therapy can effectively reduce total MDSCs (13.30 vs. 2.81, p < 0.001; 15.09 vs. 3.31, p < 0.001) and PMN-MDSCs (13.21 vs. 2.14, p < 0.001; 13.78 vs. 2.22, p < 0.001). Conclusions: This study shows that peripheral MDSCs are significantly increased and have important diagnostic value in CRC. Detection of peripheral MDSCs has a potential implication for predicting therapeutic efficacy of chemotherapy for CRC patients.