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

Abstract

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.