Wang Yang, Sun Jintang, Gao Wenjuan, Song Bingfeng, Shao Qianqian, Zhao Lei, Zhang Yun, Wang Qingjie, Zhang Yun, Qu Xun
Department of Tumor Immunity, Institute of Basic Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
Mol Med Rep. 2017 Jun;15(6):3810-3818. doi: 10.3892/mmr.2017.6482. Epub 2017 Apr 19.
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.
先前的研究表明，T细胞免疫球蛋白和粘蛋白结构域3（Tim-3）在淋巴细胞和多种癌症中发挥重要的调节作用。然而，Tim-3在各种淋巴细胞亚群上的表达与人类结直肠癌（CRC）之间的关联尚未阐明。本研究旨在表征CRC患者外周淋巴细胞上Tim-3的表达情况，这些外周淋巴细胞包括分化簇CD3⁺CD56⁻T细胞、CD3⁻CD56⁺自然杀伤（NK）细胞和CD3⁺CD56⁺自然杀伤T（NKT）细胞。通过对36例术前CRC患者和38例健康供体采集的外周血进行多色流式细胞术，评估表达Tim-3的T细胞、NK细胞和NKT细胞的频率。还分析了53例CRC患者术后血样中淋巴细胞亚群上Tim-3的表达情况。与健康对照相比，CRC患者的循环NK细胞较少（P = 0.0027）；NK细胞上Tim-3的表达也显著降低（P = 0.0239）。与健康对照相比，循环NK细胞和Tim-3⁺NK细胞的频率与临床癌症分期呈负相关，但与其他临床病理参数或CRC生物标志物的血清浓度无关。此外，无转移的CRC患者NK细胞中Tim-3的表达较高。值得注意的是，原发性肿瘤手术切除后，CRC患者NK细胞Tim-3的表达显著恢复。总之，本研究表明CRC患者外周NK细胞中Tim-3的频率和表达发生了改变。术前外周NK细胞上Tim-3的表达与结直肠癌的不同分期相关，可能作为一种血清生物标志物。
