Tumor-infiltrating regulatory T cells are positively correlated with angiogenic status in renal cell carcinoma  

作　　者：NING Hao SHAO Qian-qian DING Ke-jia GAO De-xuan LU Qing-le CAO Qing-wei NIU Zhi-hong FU Qiang ZHANG Chun-huan QU Xun LU Jia-ju 

机构地区：[1]Department of Urology, Provincial Hospital Affiliated to ShandongUniversity, Jinan, Shandong 250021, China [2]Institute of Basic Medical Sciences, Qilu Hospital, ShandongUniversity, Jinan, Shandong 250012, China [3]Department of Clinical Laboratory, Eye Ear Nose and ThroatHospital of Shandong Provincial Hospital Group, Jinan, Shandong250021,China

出　　处：《Chinese Medical Journal》2012年第12期2120-2125,共6页中华医学杂志（英文版）

基　　金：This study was supported by the grants from the National Natural Science Foundation of China （No. 81072406） and the Natural Science Foundation of Shandong Province （No. Y2006C71 and No. ZR2011HQ027）.

摘　　要：Background Immune cells within a tumor microenvironment have shown modulatory effects on tumor angiogenic activity. Renal cell carcinoma （RCC） is a hypervascular tumor that reportedly increases the frequency of regulatory T cells （Tregs） in tumor tissues. This study investigated the correlation between Tregs infiltration and angiogenic status in RCC. Methods Thirty-six patients with RCC were enrolled in the present study, and twenty age-matched healthy donors were included as the control. Tregs were defined as CD4＋CD25highCD127low/- T cells. The frequency of Tregs in peripheral blood and tumor infiltrating lymphocytes （TILs） were determined by flow cytometry. The expression of vascular endothelial growth factor （VEGF） in surgical resection specimens were measured with a commercial enzyme-linked immunosorbent assay （ELISA） kit. Microvessel density （MVD） was calculated on slides stained with CD34 antibody. Spearman＇s rank correlation was performed to evaluate the correlation between the frequencies of Tregs in TILs and VEGF values, as well as between frequencies of Tregs and MVD determinations. Results Compared to healthy controls, the frequency of peripheral blood Tregs was significantly increased in patients with RCC （P 〈0.05）. The percentage of tumor-infiltrating Tregs was higher than that of peripheral blood Tregs in patients with RCC （P 〈0.01）. In addition, the frequency of tumor-infiltrating Tregs was shown to significantly correlate with the pathological stage （P 〈0.05） and nuclear grade （P 〈0.01）. Importantly, a significant positive correlation was observed between the frequency of tumor-infiltrating Tregs and VEGF protein expression （r=0.51, P 〈0.05）, as well as between frequencies of Tregs and MVD score （r=0.39, P 〈0.05）. Conclusions These observations suggest that the high pro-angiogenic status of RCC may be associated with the accumulation of Tregs in the local microenvironment. Angiogenesis networks may be connected with immune tolerance uBackground Immune cells within a tumor microenvironment have shown modulatory effects on tumor angiogenic activity. Renal cell carcinoma （RCC） is a hypervascular tumor that reportedly increases the frequency of regulatory T cells （Tregs） in tumor tissues. This study investigated the correlation between Tregs infiltration and angiogenic status in RCC. Methods Thirty-six patients with RCC were enrolled in the present study, and twenty age-matched healthy donors were included as the control. Tregs were defined as CD4＋CD25highCD127low/- T cells. The frequency of Tregs in peripheral blood and tumor infiltrating lymphocytes （TILs） were determined by flow cytometry. The expression of vascular endothelial growth factor （VEGF） in surgical resection specimens were measured with a commercial enzyme-linked immunosorbent assay （ELISA） kit. Microvessel density （MVD） was calculated on slides stained with CD34 antibody. Spearman＇s rank correlation was performed to evaluate the correlation between the frequencies of Tregs in TILs and VEGF values, as well as between frequencies of Tregs and MVD determinations. Results Compared to healthy controls, the frequency of peripheral blood Tregs was significantly increased in patients with RCC （P 〈0.05）. The percentage of tumor-infiltrating Tregs was higher than that of peripheral blood Tregs in patients with RCC （P 〈0.01）. In addition, the frequency of tumor-infiltrating Tregs was shown to significantly correlate with the pathological stage （P 〈0.05） and nuclear grade （P 〈0.01）. Importantly, a significant positive correlation was observed between the frequency of tumor-infiltrating Tregs and VEGF protein expression （r=0.51, P 〈0.05）, as well as between frequencies of Tregs and MVD score （r=0.39, P 〈0.05）. Conclusions These observations suggest that the high pro-angiogenic status of RCC may be associated with the accumulation of Tregs in the local microenvironment. Angiogenesis networks may be connected with immune tolerance u

关 键 词：regulatory T cells renal cell carcinoma vascular endothelial growth factor ANGIOGENESIS microvessel density 

分 类 号：R737.11[医药卫生—肿瘤]