Hojo Shozo, Koizumi Keiichi, Tsuneyama Koichi, Arita Yoshihisa, Cui Zhengguo, Shinohara Kanna, Minami Takayuki, Hashimoto Isaya, Nakayama Takashi, Sakurai Hiroaki, Takano Yasuo, Yoshie Osamu, Tsukada Kazuhiro, Saiki Ikuo
Department of Surgery (II), Institute of Natural Medicine, University of Toyama, Toyama, Japan.
Cancer Res. 2007 May 15;67(10):4725-31. doi: 10.1158/0008-5472.CAN-06-3424.
CXCL16 is a new member of the chemokine superfamily, which exists in a transmembrane as well as a soluble form. Its receptor CXCR6 is detected on CD4(+) T cells, CD8(+) T cells, and natural killer T cells. Here, we report a significant correlation of CXCL16 expression by tumor cells with the infiltration of T cells and prognosis in colorectal cancer (CRC). We first found that CXCL16 expression was consistently up-regulated more in tumor tissues than in normal mucosa derived from the same CRC patients. Four human CRC cell lines also expressed CXCL16 mRNA and secreted soluble CXCL16. We next examined the expression of CXCL16 and infiltration of lymphocytes in CRC specimens (n = 58) by immunohistochemistry. CRC patients with high levels of CXCL16 expression (n = 43) had higher levels of CD4(+) and CD8(+) tumor-infiltrating lymphocytes (TIL; P < 0.01) than those with low levels of CXCL16 expression (n = 15). Furthermore, the high CXCL16 expression group showed significantly better prognosis than the low CXCL16 expression group (P < 0.05). Collectively, our data suggest that the expression of CXCL16 by tumor cells enhances the recruitment of TILs, thereby bringing about a better prognosis in CRC. Thus, CXCL16 is a new prognostic biomarker and may be useful for the development of a more effective therapeutic strategy for CRC.
CXCL16是趋化因子超家族的新成员，以跨膜形式和可溶性形式存在。其受体CXCR6在CD4(+)T细胞、CD8(+)T细胞和自然杀伤T细胞上被检测到。在此，我们报告肿瘤细胞CXCL16表达与结直肠癌（CRC）中T细胞浸润及预后显著相关。我们首先发现，与来自相同CRC患者的正常黏膜相比，肿瘤组织中CXCL16表达持续上调更多。四种人CRC细胞系也表达CXCL16 mRNA并分泌可溶性CXCL16。接下来，我们通过免疫组织化学检查了58例CRC标本中CXCL16的表达和淋巴细胞浸润情况。CXCL16高表达的CRC患者（n = 43）比CXCL16低表达的患者（n = 15）具有更高水平的CD4(+)和CD8(+)肿瘤浸润淋巴细胞（TIL；P < 0.01）。此外，CXCL16高表达组的预后明显优于CXCL16低表达组（P < 0.05）。总体而言，我们的数据表明肿瘤细胞CXCL16的表达增强了TIL的募集，从而使CRC患者预后更好。因此，CXCL16是一种新的预后生物标志物，可能有助于开发更有效的CRC治疗策略。
