Concentrations of TIM-3 protein and its ligand Galectin-9 in patients with colorectal cancer

Abstract

Background. Recent studies have demonstrated that the membrane protein TIM-3 and its ligand Galectin-9 play an important role in the escape of tumor cells from immune surveillance and in the progression of the malignant process. Aim. To assess the concentrations of TIM-3 and Galectin-9 in blood serum, tumor tissue, and in lymph nodes of patients with colon neoplasms. Methods. The study included 44 patients with colorectal cancer (CRC) and 25 patients with benign colon tumors. The control group consisted of 25 patients who had had a scheduled surgery (plastic colostomy). The concentrations of TIM-3 and Galectina-9 were determined in serum, as well as in the supernatant of tumour and lymph node homogenates by flow cytometry using a CytoFlex LX (Beckman Coulter, USA) analyzer with LEGENDplex™ HU (Immune Checkpoint, USA) kits for multiplex assays. The non-parametric Mann-Whitney test was used to determine statistical significance of differences. Results. The serum concentration of TIM-3 was 11.7 times higher in patients with CRC than in the control group (p < 0.001) and 7.1 times higher than in patients with benign tumors (p < 0.001). The concentration of TIM-3 in tumor tissue in the CRC patients with was 43.6 times higher than in the control group (p < 0.001) and 11.4 times higher than in patients with benign tumors of the colon (p < 0.001). The serum concentration of Galectin-9 in patients with CRC was 33.3 times higher than in the control group (p < 0.001) and 4.4 times higher than in the group with benign tumors (p < 0.001). More pronounced changes in this protein’s increase were noted in the tumor tissue. The concentration of TIM-3 in lymph node tissue in patients with CRC was 8447.5 pg/ml, the Galectina-9 concentration was 9289.7 pg/ml. Conclusion. The data obtained demonstrate a marked increase in the level of TIM-3 and its Galectin-9 ligand in blood serum and tumor tissue in patients with CRC, as well as their direct correlation with each other. This suggests that these proteins contribute to the pathogenesis of tumor cell escape from immune surveillance in CRC.