State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen (Zhongshan) University, Guangzhou, 510 060, People's Republic of China.
Cancer Immunol Immunother. 2013 Oct;62(10):1575-85. doi: 10.1007/s00262-013-1460-4. Epub 2013 Aug 3.
The proinflammatory cytokine interleukin 17 (IL-17) is considered to play a crucial role in diverse human tumors; however, its role in disease progression remains controversial. This study investigated the cellular source and distribution of IL-17 in esophageal squamous cell carcinoma (ESCC) in situ and determined its prognostic value. Immunohistochemistry, immunofluorescence and immunoelectron microscopy were used to identify IL-17-expressing cells in ESCC tissues, paying particular attention to their anatomic localization. Kaplan-Meier analysis and Cox proportional hazards regression models were applied to estimate overall survival in 215 ESCC patients with long-term follow-up (>10 years). The results showed that mast cells, but not T cells or macrophages, were the predominant cell type expressing IL-17 in ESCC tissues. Unexpectedly, these IL-17(+) cells were highly enriched in the muscularis propria rather than the corresponding tumor nest (p < 0.0001). The density of IL-17(+) cells in muscularis propria was inversely associated with tumor invasion (p = 0.016) and served as an independent predictor of favorable survival (p = 0.007). Moreover, the levels of IL-17(+) cells in muscularis propria were positively associated with the density of effector CD8(+) T cells and activated macrophages in the same area (both p < 0.0001). This finding suggested that mast cells may play a significant role in tumor immunity by releasing IL-17 at a previously unappreciated location, the muscularis propria, in ESCC tissues, which could serve as a potential prognostic marker and a novel therapeutic target for ESCC.
促炎细胞因子白细胞介素 17（IL-17）被认为在多种人类肿瘤中发挥关键作用；然而，其在疾病进展中的作用仍存在争议。本研究调查了食管鳞状细胞癌（ESCC）原位中 IL-17 的细胞来源和分布，并确定了其预后价值。免疫组织化学、免疫荧光和免疫电子显微镜用于鉴定 ESCC 组织中表达 IL-17 的细胞，特别注意其解剖定位。Kaplan-Meier 分析和 Cox 比例风险回归模型用于估计 215 例具有长期随访（>10 年）的 ESCC 患者的总生存率。结果表明，肥大细胞而不是 T 细胞或巨噬细胞是 ESCC 组织中表达 IL-17 的主要细胞类型。出乎意料的是，这些 IL-17(+)细胞在肌层中高度富集，而不是相应的肿瘤巢（p < 0.0001）。肌层中 IL-17(+)细胞的密度与肿瘤侵袭呈负相关（p = 0.016），并作为有利生存的独立预测因子（p = 0.007）。此外，肌层中 IL-17(+)细胞的密度与同一区域中效应性 CD8(+)T 细胞和活化巨噬细胞的密度呈正相关（均 p < 0.0001）。这一发现表明，肥大细胞可能通过在 ESCC 组织中以前未被认识到的位置——肌层释放 IL-17，在肿瘤免疫中发挥重要作用，这可能成为 ESCC 的一个潜在预后标志物和新的治疗靶点。
