Preoperative Tim-3 expression on peripheral NK cells is correlated with pathologic TNM staging in colorectal cancer

Previous research has indicated that T cell immunoglobulin and mucin domain 3 (Tim-3) serves an important regulatory role in lymphocytes and in several cancers. However, the association between Tim-3 expression on various lymphocyte subsets and human colorectal cancer (CRC) has not been elucidated. The present study aimed to characterize Tim-3 expression on peripheral lymphocytes, including cluster of differentiation CD3(+)CD56-T cells, CD3 CD56(+) natural killer (NK) cells and CD3(+)CD56(+) natural killer T (NKT) cells, in patients with CRC. The frequency of T cells, NK cells and NKT cells expressing Tim-3 was assessed by multicolor flow cytometry of peripheral blood collected from 36 preoperative CRC patients and 38 healthy donors. The expression of Tim-3 on lymphocyte subsets from 53 postoperative blood samples of CRC patients was also analyzed. There were fewer circulating NK cells in patients with CRC compared with healthy controls (P=0.0027); NK cell expression of Tim-3 was also significantly decreased (P=0.0239). The frequency of circulating NK cells and Tim-3(+) NK cells was negatively correlated with clinical cancer stage, compared with healthy controls, but not with other clinicopathological parameters or serum concentrations of CRC biomarkers. Furthermore, the expression of Tim-3 in NK cells was higher in CRC patients without metastasis. Notably, NK cell Tim-3 expression in CRC patients was significantly restored following surgical resection of the primary tumor. In conclusion, the present study indicates the presence of an altered frequency and expression of Tim-3 in peripheral NK cells in CRC patients. Preoperative Tim-3 expression on peripheral NK cells is correlated with differential staging in colorectal cancer, and may be useful as a serum biomarker.