The high expression of Fractalkine results in a better prognosis for colorectal cancer patients.

The high expression of Fractalkine results in a better prognosis for colorectal cancer patients.
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DOI:
10.3892/ijo.26.1.41
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发表时间:
2005
影响因子:
5.2
通讯作者:
Mitsuhiko Ohta;F. Tanaka;H. Yamaguchi;N. Sadanaga;H. Inoue;M. Mori
Mitsuhiko Ohta;F. Tanaka;H. Yamaguchi;N. Sadanaga;H. Inoue;M. Mori
中科院分区:
医学2区
文献类型:
--
作者:
Mitsuhiko Ohta;F. Tanaka;H. Yamaguchi;N. Sadanaga;H. Inoue;M. Mori

文献摘要

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结直肠癌(CRC)患者的局部和全身免疫反应受损,肿瘤浸润性淋巴细胞(TIL)数量较少。另一方面,部分TIL较多的结直肠癌患者的生存期较少TIL的患者长。近年来,趋化因子与肿瘤细胞之间的关系受到了广泛的关注。一些趋化因子为肿瘤病变招募淋巴细胞。我们假设Fractalkine是一种CX3C趋化因子,可以在结直肠癌中募集淋巴细胞,在抗肿瘤免疫中发挥重要作用。我们分析了Fractalkine在结直肠癌细胞系以及临床标本中的表达水平(n=80)。因此,Fractalkine的表达水平与TIL的密度相关(p<0.05)。Fractalkine强表达组(n=50)的预后明显好于弱表达组(n=30)(p<0.05)。此外,Fractalkine的表达被发现是一个独立的预后因素(p<0.05)。我们进一步明确了部分肿瘤浸润性细胞是自然杀伤细胞和表达Fractalkine受体的细胞毒性T细胞。这些结果提示,在肿瘤中表达的Fractalkine似乎能将细胞毒性T细胞和NK细胞聚集到肿瘤部位,这些细胞毒细胞通过穿孔素和颗粒酶B机制介导的肿瘤细胞毒性导致更好的预后。Fractalkine的表达水平是预测结直肠癌患者预后的重要生物标志物。Fractalkine被认为是检测高复发风险患者的生物标志物之一,因此他们可能会从辅助治疗等额外治疗策略中受益。
Local and systemic immune responses are impaired in patients with colorectal cancer (CRC) and it is known that the number of tumor infiltrating lymphocytes (TILs) is considerably few. On the other hand, some CRC cases in which many TIL were observed, survived longer than those cases with a small number of TIL. Considerable attention has been recently paid to the relationship between chemokines and tumor cells. Some chemokines recruit lymphocytes for tumor lesions. We made a hypothesis that Fractalkine, a CX3C chemokine, would recruit lymphocytes in the CRC and play an important role in anti-tumor immunity. We analyzed the expression level of Fractalkine in CRC cell lines as well as in clinical samples (n=80). The expression level of Fractalkine was thus found to correlate with the density of TIL (p<0.05). The CRC cases with a strong Fractalkine expression (n=50) showed a significantly better prognosis than those with a weak expression (n=30) (p<0.05). In addition, the Fractalkine expression was found to be an independent prognostic factor (p<0.05). We furthermore clarified that some of the tumor-infiltrating cells were natural killer cells and cytotoxic T cells expressed Fractalkine receptor. These data suggest that Fractalkine expressed in the tumor appears to recruit cytotoxic T cells and NK cells to the tumor site and these cytotoxic cells result in a better prognosis mediated by tumor cell cytotoxicity using a perforin and granzyme B mechanism. The expression level of Fractalkine was an essential biomarker for predicting the prognosis of patients with CRC. Fractalkine is considered to be one of the biomarkers for detecting patients with a high risk for recurrence, and who might therefore benefit from additional therapeutic strategies such as adjuvant therapy.