Mast Cells Comprise the Major of Interleukin 17-Producing Cells and Predict a Poor Prognosis in Hepatocellular Carcinoma

Abstract

IL-17 and IL-17-producing cells have been found in many types of human cancers and murine models. However, the source of tumor-infiltrating IL-17 and IL-17-producing cells in HCC and the prognostic values remain poorly understood.A total of 57 HCC patients were enrolled in this study, and immunofluorescence double stain was used to evaluate the colocalization of CD3+ T cells, CD4+ T cells, CD56+ NK cells, CD20+ B cells, CD68+ Macrophages, and MCT+ mast cells with IL-17. The prognostic value of IL-17-producing cells was evaluated by Kaplan–Meier analysis and Cox regression model.MCT+ mast cells, but not other cells, were the predominant IL-17-producing cell type. Overall survival analysis revealed that the increasing intratumoral-infiltrated MCT+ mast cells were significantly associated with poor prognosis. Immunofluorescence double stain showed a positive correlation between the number of MCT+ mast cells and MCVs.These findings indicated the major IL-17-producing cells in HCC were MCT+ mast cells and these cells infiltration may promote tumor progression by angiogenesis. Increased MCT+ mast cells was associated with a poor prognosis, indicating therapy targeting MCT+ mast cells might be an effective strategy in controlling intratumor IL-17 infiltration and MCVs.

Tumor‐infiltrating tryptase+ mast cells predict unfavorable clinical outcome in solid tumors

“…Literature searches yield 11,417 records and the results were shown in Figure S1. Twenty eight studies containing 4,224 patients with solid tumor were identified for the assessment of tumor‐infiltrating tryptase + mast cells . All the studies were evaluated by the Newcastle–Ottawa Scale (NOS), and were in accordance with the inclusion criteria and suitable for data consolidation.…”

Immunity and Fibrogenesis: The Role of Th17/IL-17 Axis in HBV and HCV-induced Chronic Hepatitis and Progression to Cirrhosis

“…Besides the Th17 cells, recent investigations have found other immune cells, such as mast cells, and neutrophils as important sources of IL-17 in CVH, especially in late fibrosis stages ( 66 – 68 ). These findings emerge in a context after many studies have shown the domain of neutrophils as a predictor of outcomes in viral hepatitis and related diseases ( 19 , 41 ).…”

Applying Machine Learning in Liver Disease and Transplantation: A Comprehensive Review

“…This is especially powerful when there are many interactions between the predictors and when data are high‐dimensional, which is certainly reflected in the complexity of liver diseases. MLAs have been shown to improve precision in identifying individuals at risk of disease …”

“…MLAs have been shown to improve precision in identifying individuals at risk of disease. (5)(6)(7)(8)(9)(10)…”