High infiltration of mast cells is associated with improved response to adjuvant chemotherapy in gallbladder cancer
High infiltration of mast cells is associated with improved response to adjuvant chemotherapy in gallbladder cancer
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肥大细胞的高浸润与胆囊癌辅助化疗反应的改善相关
DOI：
10.1111/cas.14302
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发表时间：
2020-02-03
期刊：
影响因子：
5.7
通讯作者：
Liu, Houbao
中科院分区：
文献类型：
--
作者：
Bo, Xiaobo;Wang, Jie;Liu, Houbao
近年来的研究表明，肿瘤浸润性肥大细胞（TIM）在肿瘤消退中起重要作用，但TIM在胆囊癌（GBC）中的作用尚不清楚。本研究旨在探讨TIM在GBC患者中的预后价值及其对吉西他滨辅助化疗（ACT）的反应性。本研究共收集了298例来自中山医院的GBC患者。免疫组化染色检测TIM浸润情况。TIM的积累与GBC患者的总生存期延长显著相关。在伴有GBC的TIM高浸润患者中，基于吉西他滨的ACT的获益为上级。多因素分析表明TIM浸润是影响总生存率的独立预后因素。热图显示TIM激活的基因签名与CD8+ T细胞的基因签名正相关。基因集富集分析（GSEA）提示TIM与多种T细胞相关过程和信号通路有关，包括干扰素γ信号通路和白细胞迁移信号通路。组织芯片（TMA）结果显示，GBC中CD8+ T细胞浸润与高TIM浸润呈正相关，提示GBC中TIM浸润与免疫监视有关。TIM可用作GBC患者中吉西他滨为基础的ACT的独立预后因素和治疗应答的预测因子，其可通过募集和激活GBC中的CD8+ T细胞介导免疫监视。
Recent studies have reported that tumor-infiltrating mast cells (TIM) play an important role in tumor regression, but the effect of TIM in gallbladder cancer (GBC) remains unclear. The present study aims to investigate the prognostic value of TIM in GBC patients and its responsiveness to gemcitabine-based adjuvant chemotherapy (ACT). A total of 298 GBC patients from Zhongshan Hospital were recruited for this study. TIM infiltration was measured by immunohistochemical staining. Accumulation of TIM is significantly associated with prolonged overall survival in GBC patients. The benefit from gemcitabine-based ACT was superior among patients with high infiltration of TIM with GBC. Multivariate analysis identified TIM infiltration as an independent prognostic factor for overall survival. A heatmap showed that TIM-activated gene signatures were positively correlated with CD8+ T cells' gene signatures. Gene set enrichment analysis (GSEA) suggested that TIM was related to multiple T cell-related processes and signaling pathways, including the interferon gamma signaling pathway and the leukocyte migration signaling pathway. It was confirmed that CD8+ T cell infiltration was positively correlated with high TIM infiltration in tissue microarray (TMA), suggesting that TIM infiltration was linked to the immune surveillance in GBC. TIM can be used as an independent prognostic factor and a predictor of therapeutic response of gemcitabine-based ACT in GBC patients, which may mediate immune surveillance by recruiting and activating CD8+ T cells in GBC.