Hu Min, Li Kai, Maskey Ninu, Xu Zhigao, Peng Chunwei, Wang Bicheng, Li Yan, Yang Guifang
Department of Pathology, Zhongnan Hospital of Wuhan University Wuhan 430071, China.
Department of Oncology, Zhongnan Hospital of Wuhan University Wuhan 430071, China.
Int J Clin Exp Pathol. 2014 Jul 15;7(8):4685-94. eCollection 2014.
Although neoadjuvant chemotherapy (NACT) has been increasingly used to improve the outcome of advanced gastric cancer (GC) for decades, its precise efficacy has been difficult to evaluate yet. Abundant studies have investigated the predictive factors that represent the effect of NACT on advanced GC. In the present study, the intratumoral infiltration of regulatory T cells (Tregs) and dendritic cells (DCs) response to NACT in advanced GC and their correlation with prognosis were evaluated. Infiltration of Tregs (marked by Foxp3) and DCs (marked by S-100) in 102 advanced GC specimens with or without NACT was measured using immunohistochemical method. Intratumoral infiltration of Foxp3 Tregs was significantly lower and DC density was significantly higher in NACT group than that in nNACT group (P=0.007, P=0.002, respectively). Infiltration of Foxp3 Tregs was significantly associated with tumor invasion depth (P<0.001). The DC density was significantly correlated with histopathologic type (P=0.035), invasion depth (P=0.002), TNM stage (P=0.018), and lymph node metastasis (P<0.001). There was no significant difference of patient's OS between NACT and nNACT groups (P=0.452); however, patients treated with NACT had longer OS with lower infiltration of Foxp3 Tregs (P<0.001) and higher infiltration of DCs (P=0.010). Univariate and multivariate analyses indicated that infiltration of Foxp3 Tregs and DCs were independent prognostic factors (P=0.002, P=0.003, respectively). The results demonstrated that NACT could decrease intratumoral Foxp3 Tregs infiltration and increase DCs density, and that infiltration of Foxp3 Tregs and DCs may serve as novel prognostic biomarkers of human GC.
尽管数十年来新辅助化疗（NACT）已越来越多地用于改善晚期胃癌（GC）的治疗效果，但其确切疗效仍难以评估。大量研究已对代表NACT对晚期GC疗效的预测因素进行了调查。在本研究中，评估了晚期GC中调节性T细胞（Tregs）的瘤内浸润以及树突状细胞（DCs）对NACT的反应及其与预后的相关性。采用免疫组织化学方法检测了102例接受或未接受NACT的晚期GC标本中Tregs（以Foxp3标记）和DCs（以S-100标记）的浸润情况。NACT组瘤内Foxp3 Tregs浸润显著低于未接受NACT组（nNACT组），DC密度显著高于nNACT组（分别为P = 0.007，P = 0.002）。Foxp3 Tregs浸润与肿瘤浸润深度显著相关（P < 0.001）。DC密度与组织病理学类型（P = 0.035）、浸润深度（P = 0.002）、TNM分期（P = 0.018）及淋巴结转移（P < 0.001）显著相关。NACT组和nNACT组患者的总生存期（OS）无显著差异（P = 0.452）；然而，接受NACT治疗的患者OS更长，其Foxp3 Tregs浸润较低（P < 0.001）且DC浸润较高（P = 0.010）。单因素和多因素分析表明，Foxp3 Tregs和DCs浸润是独立的预后因素（分别为P = 0.002，P = 0.003）。结果表明，NACT可降低瘤内Foxp3 Tregs浸润并增加DC密度，且Foxp3 Tregs和DCs浸润可能作为人类GC新的预后生物标志物。
