title: Mast cells expressing interleukin 17 in the muscularis propria predict a favorable prognosis in esophageal squamous cell carcinoma.
abstract: 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.
authors.affiliation: State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen (Zhongshan) University, Guangzhou, 510 060, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.forename: Lian
authors.initials: L
authors.lastname: Li
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liao
authors.forename: Jinqing
authors.initials: J
authors.lastname: Li
authors.forename: Xingjuan
authors.initials: X
authors.lastname: Yu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Huilan
authors.initials: H
authors.lastname: Rao
authors.forename: Shupeng
authors.initials: S
authors.lastname: Chen
authors.forename: Lanjun
authors.initials: L
authors.lastname: Zhang
authors.forename: Limin
authors.initials: L
authors.lastname: Zheng
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000276:immunology; D008262:Macrophage Activation / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; D020381:Interleukin-17
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