Intratumor IL-17-positive mast cells are the major source of the IL-17 that is predictive of survival in gastric cancer patients.
Intratumor IL-17-positive mast cells are the major source of the IL-17 that is predictive of survival in gastric cancer patients.
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肿瘤内 IL-17 阳性肥大细胞是 IL-17 的主要来源，可预测胃癌患者的生存。
DOI：
10.1371/journal.pone.0106834
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Yu J
中科院分区：
文献类型：
--
作者：
Liu X;Jin H;Zhang G;Lin X;Chen C;Sun J;Zhang Y;Zhang Q;Yu J
白介素 17 (IL-17) 普遍存在于肿瘤组织中，可抑制有效的抗肿瘤免疫反应。然而，肿瘤浸润性 IL-17 增加的来源及其对人类胃癌肿瘤进展的贡献仍知之甚少。在这项研究中，我们招募了 112 名胃癌患者，使用免疫荧光评估 CD3、CD4、CD56、CD20、CD68 和肥大细胞类胰蛋白酶 (MCT) 与 IL-17 的共定位。采用免疫组织化学方法评估微血管密度（CD34）、CD66b+、CD68+和FoxP3+细胞在不同显微解剖区域的分布。预后价值由 Kaplan-Meier 分析和 Cox 回归模型确定。结果表明，肥大细胞，而非 T 细胞或巨噬细胞，是胃癌中产生 IL-17 的主要细胞类型。肥大细胞来源的 IL-17 与微血管、中性粒细胞和调节性 T 细胞 (Treg) 的密度之间检测到显着的正相关性。此外，我们发现大多数血管内皮细胞表达白介素17受体（IL-17R）。 Kaplan-Meier 分析显示，肿瘤内浸润的肥大细胞和 IL-17+ 细胞以及 MCT+ IL-17+ 细胞的增加与较差的总体生存率显着相关。这些发现表明肥大细胞是胃癌中IL-17的主要来源，肿瘤内IL-17浸润可能通过IL-17/IL-17R轴增强肿瘤微环境中的血管生成来促进肿瘤进展。 IL-17阳性肥大细胞在胃癌中显示出预后因素，表明针对肥大细胞的免疫治疗可能是控制肿瘤内IL-17浸润的有效策略，从而逆转肿瘤微环境中的免疫抑制，促进癌症免疫治疗。
Interleukin-17 (IL-17) is prevalent in tumor tissue and suppresses effective anti-tumor immune responses. However, the source of the increased tumor-infiltrating IL-17 and its contribution to tumor progression in human gastric cancer remain poorly understood. In this study, we enrolled 112 gastric cancer patients, immunofluorescence was used to evaluate the colocalization of CD3, CD4, CD56, CD20, CD68, and mast cell tryptase (MCT) with IL-17. Immunohistochemistry was used to evaluate the distribution of microvessel density (CD34), CD66b+, CD68+, and FoxP3+ cells in different microanatomical areas. Prognostic value was determined by Kaplan-Meier analysis and a Cox regression model. The results showed that mast cells, but not T cells or macrophages, were the predominant cell type producing IL-17 in gastric cancer. Significant positive correlations were detected between densities of mast cell-derived IL-17 and microvessels, neutrophils, and regulatory T cells (Tregs). Futhermore, we found that the majority of vascular endothelial cells expressing Interleukin-17 receptor (IL-17R). Kaplan-Meier analysis revealed that increasing intratumor infiltrated mast cells and IL-17+ cells, as well as MCT+ IL-17+ cells, were significantly associated with worse overall survival. These findings indicated that mast cells were the major source of IL-17 in gastric cancer, and intratumor IL-17 infiltration may have promoted tumor progression by enhancing angiogenesis in the tumor microenvironment through the axis of IL-17/IL-17R. IL-17-positive mast cells showed a prognostic factor in gastric cancer, indicating that immunotherapy targeting mast cells might be an effective strategy to control intratumor IL-17 infiltration, and consequently reverse immunosuppression in the tumor microenvironment, facilitating cancer immunotherapy.
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DOI：
10.4049/jimmunol.1102389
发表时间：
2012-01-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ganeshan K;Bryce PJ
通讯作者：
Bryce PJ
DOI：
10.4049/jimmunol.1100123
发表时间：
2011-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Lin AM;Rubin CJ;Khandpur R;Wang JY;Riblett M;Yalavarthi S;Villanueva EC;Shah P;Kaplan MJ;Bruce AT
通讯作者：
Bruce AT
影响因子：
3.7
作者：
Gu, Fang-Ming;Gao, Qiang;Zhou, Jian
通讯作者：
Zhou, Jian
影响因子：
15.9
作者：
Blair, RJ;Meng, H;Gruber, BL
通讯作者：
Gruber, BL
影响因子：
20.3
作者：
Kryczek, Ilona;Banerjee, Mousumi;Zou, Weiping
通讯作者：
Zou, Weiping