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B7-H3 in combination with regulatory T cell is associated with tumor progression in primary human non-small cell lung cancer
Authors:Yingjie Jin  Pei Zhang  Juan Li  Jianqiang Zhao  Chuanyong Liu  Fei Yang  Dong Yang  Aiqin Gao  Wenli Lin  Xiaoxia Ma  Yuping Sun
Affiliation:1Department of Oncology, Jinan Central Hospital, Shandong University, Jinan 250013, Shandong, P. R. China;2Department of Oncology, Zhangqiu Hospital, Zhangqiu, 250200, Shandong, P. R. China;3Department of Pathology, Jinan Central Hospital, Shandong University, Jinan 250013, Shandong, P. R. China;4Department of Gastroscopy Center, Jinan Central Hospital, Shandong University, Jinan 250013, Shandong, P. R. China
Abstract:B7-H3 belongs to the co-inhibitory B7 family and plays an important role in the adaptive immune response in regulating T cells. In human malignancies, B7-H3 is reported to be involved in tumor immune evasion. However, the detailed molecular mechanism of B7-H3 in tumor evasion remains unclear, particularly in non-small cell lung cancer (NSCLC). Regulatory T cells (Tregs) are known as a key player in the inhibition of immune mechanisms. The study demonstrated the correlation between B7-H3 on tumor cells and the number of Tregs in the tumor microenvironment in NSCLC. B7-H3 was examined in tumor tissues from 110 patients with NSCLC by immunohistochemical analysis. Forkhead box P3+ (FOXP3+) Tregs in those spencimens were also detected and numbered. Survival curves were drawn using the Kaplan-Meier method and compared by the log-rank test. High B7-H3 expression in tumor cells significantly correlated with male gender, squamous NSCLC, advanced stage and shorter overall survival (OS) (P = 0.035, P = 0.004, P = 0.037, P = 0.014, respectively). Meanwhile, FOXP3 expression in tumor-infiltrating lymphocytes (TILs) was associated with male gender, regional lymph node involvement, advanced stage and worse OS (P = 0.009, P = 0.015, P = 0.014, P = 0.034, respectively). Significant correlation was identified between the expression of B7-H3 and the number of FOXP3+ TILs (P = 0.013). Patients with B7-H3 high/FOXP3 high had poorer OS (P = 0.006), suggesting that B7-H3 and Tregs may play a cooperatively role in tumor immune evasion, leading to poor outcomes for NSCLC patients.
Keywords:B7-H3   regulatory T cell   tumor immune evasion   non-small cell lung cancer
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