Jin Yingjie, Zhang Pei, Li Juan, Zhao Jianqiang, Liu Chuanyong, Yang Fei, Yang Dong, Gao Aiqin, Lin Wenli, Ma Xiaoxia, Sun Yuping
Department of Oncology, Jinan Central Hospital, Shandong UniversityJinan 250013, Shandong, P. R. China; Department of Oncology, Zhangqiu HospitalZhangqiu, 250200, Shandong, P. R. China.
Department of Oncology, Jinan Central Hospital, Shandong University Jinan 250013, Shandong, P. R. China.
Int J Clin Exp Pathol. 2015 Nov 1;8(11):13987-95. eCollection 2015.
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.
B7-H3属于共抑制性B7家族，在调节T细胞的适应性免疫反应中发挥重要作用。在人类恶性肿瘤中，据报道B7-H3参与肿瘤免疫逃逸。然而，B7-H3在肿瘤逃逸中的详细分子机制仍不清楚，尤其是在非小细胞肺癌（NSCLC）中。调节性T细胞（Tregs）是免疫机制抑制中的关键参与者。该研究证明了NSCLC肿瘤微环境中肿瘤细胞上的B7-H3与Tregs数量之间的相关性。通过免疫组织化学分析检测了110例NSCLC患者肿瘤组织中的B7-H3。还检测并计数了这些标本中的叉头框P3+（FOXP3+）Tregs。使用Kaplan-Meier方法绘制生存曲线，并通过对数秩检验进行比较。肿瘤细胞中高B7-H3表达与男性、鳞状NSCLC、晚期和较短的总生存期（OS）显著相关（分别为P = 0.035、P = 0.004、P = 0.037、P = 0.014）。同时，肿瘤浸润淋巴细胞（TILs）中的FOXP3表达与男性、区域淋巴结受累、晚期和较差的OS相关（分别为P = 0.009、P = 0.015、P = 0.014、P = 0.034）。B7-H3表达与FOXP3+ TILs数量之间存在显著相关性（P = 0.013）。B7-H3高/FOXP3高的患者OS较差（P = 0.006），表明B7-H3和Tregs可能在肿瘤免疫逃逸中协同发挥作用，导致NSCLC患者预后不良。
