Liu Jinyan, Li Feng, Ping Yu, Wang Liping, Chen Xinfeng, Wang Dan, Cao Ling, Zhao Song, Li Bing, Kalinski Pawel, Thorne Stephen H, Zhang Bin, Zhang Yi
Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, P.R. China.
Oncotarget. 2015 Sep 22;6(28):24978-89. doi: 10.18632/oncotarget.4617.
Esophageal squamous cell carcinoma (ESCC) is a very common malignant tumor with poor prognosis in China. Chemokines secreted by tumors are pivotal for the accumulation of CD8(+) T lymphocytes within malignant lesions in several types of cancers, but the exact mechanism underlying CD8(+) T lymphocyte homing is still unknown in ESCC. In this study, we revealed that, compared with marginal tissues, the expression of both chemokine (C-C motif) ligand 5 (CCL5) and (C-X-C motif) ligand 10 (CXCL10) was upregulated in ESCC tissues. CCL5 expression was positively associated with the overall survival of patients. Meanwhile, RT-PCR data showed that the expression of CCL5 and CXCL10 was positively correlated with the local expressions of the CD8(+) T lymphocyte markers (CD8 and Granzyme B) in tumor tissues. Correspondingly, CD8(+) T lymphocytes were more frequently CCR5- and CXCR3-positive in tumor than in peripheral blood. Transwell analysis showed both CCL5 and CXCL10 were important for the chemotactic movement of CD8(+) T lymphocytes. Our data indicate that CCL5 and CXCL10 serve as the key chemokines to recruit CD8(+) T lymphocytes into ESCC tissue and may play a role in patient survival.
食管鳞状细胞癌（ESCC）是中国一种非常常见且预后较差的恶性肿瘤。肿瘤分泌的趋化因子对于几种类型癌症中恶性病变内CD8(+) T淋巴细胞的聚集至关重要，但ESCC中CD8(+) T淋巴细胞归巢的确切机制仍不清楚。在本研究中，我们发现，与边缘组织相比，趋化因子（C-C基序）配体5（CCL5）和（C-X-C基序）配体10（CXCL10）在ESCC组织中的表达均上调。CCL5表达与患者的总生存期呈正相关。同时，逆转录聚合酶链反应（RT-PCR）数据显示，CCL5和CXCL10的表达与肿瘤组织中CD8(+) T淋巴细胞标志物（CD8和颗粒酶B）的局部表达呈正相关。相应地，肿瘤中CD8(+) T淋巴细胞CCR5和CXCR3阳性的频率高于外周血。Transwell分析表明，CCL5和CXCL10对CD8(+) T淋巴细胞的趋化运动都很重要。我们的数据表明，CCL5和CXCL10作为关键趋化因子，将CD8(+) T淋巴细胞募集到ESCC组织中，并可能在患者生存中发挥作用。
