Abstract
PURPOSE: Increased level of circulating myeloid -derived suppressor cells (MDSCs) in colorectal cancer (CRC) patients has been associated with higher tumor stage and poorer survival due to poorer response to therapeutic agents. However, studies reported inconsistent results on how chemotherapeutic agents affecting the depletion of two major types of MDSCs, polymophonuclear MDSC (PMN-MDSC) and monocytic MDSC (M-MDSC). The present study aims to learn deeper on the dynamic changes of circulating MDSCs, especially in response to oxaliplatin-based treatment in CRC patients. METHODS: This was a prospective study that recruited 30 treatment-naive patients with varying stages of CRC who were scheduled to receive oxaliplatin-based chemotherapy. Blood sampling was conducted prior to and at several time points during and after chemotherapy. Multicolor flow cytometry assay was used to analyse the proportion of HLA-DR(-) and CD33(+) with CD15(+) (PMN-MDSCs) or CD14(+) (M-MDSCs) cells within peripheral blood mononuclear cells (PBMCs). Other essential tumor biomarkers such as carcinoembryonic antigen (CEA) and tumor-infiltrating lymphocytes (TILs) were also assessed. As a control, 14 healthy subjects were recruited in this study. RESULTS: Indonesian treatment-naive CRC patients exhibited significantly higher circulating PMN-MDSCs compared to healthy subjects (p = 0.003), while M-MDSCs levels showed no significant difference between the groups (p = 0.890). Following chemotherapy, the MDSCs level demonstrated dynamic changes. Interestingly, a subgroup of CRC patients with decreased in both PMN- and M-MDSCs levels on D-14 of chemotherapy consistently showed a significant reduction in MDSCs levels during and after therapy completion compared to baseline (p = 0.0078). CONCLUSIONS: Circulating MDSCs level, particularly PMN-MDSCs, in CRC patients, was significantly higher compared to healthy subjects. Changes in both circulating PMN- and M-MDSCs levels at D-14 chemotherapy might have prognostic value in oxaliplatin-based chemotherapy.