IL‐26 promotes the pathogenesis of malignant pleural effusion by enhancing CD4+IL‐22+ T‐cell differentiation and inhibiting CD8+ T‐cell cytotoxicity

• Published in: Journal of leukocyte biology Vol. 110; no. 1; pp. 39 - 52
• Main Authors: Niu, Yiran, Ye, Linlin, Peng, Wenbei, Wang, Zihao, Wei, Xiaoshan, Wang, Xu, Li, Yu, Zhang, Siyu, Xiang, Xuan, Zhou, Qiong
• Format: Journal Article
• Language: English
• Published: England 01.07.2021
• Subjects: Biomarkers; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cell Differentiation - immunology; Cytokines - metabolism; Cytotoxicity, Immunologic; Humans; Interleukin-22; Interleukins - metabolism; Interleukin‐26; Lymphocyte Activation; Malignant pleural effusion; Nuclear Receptor Subfamily 1, Group F, Member 3 - metabolism; Pleural Effusion, Malignant - etiology; Pleural Effusion, Malignant - metabolism; Pleural Effusion, Malignant - pathology; T cell; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; Interleukin-26; Malignant pleural effusion; Interleukin-22; T cell
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1002/JLB.1MA0221-479RR

IL‐26 is a newly discovered IL‐10 cytokine family member mainly secreted by Th17 cells. However, the relationship between IL‐26 and lung cancer remains unclear. The present study reported that IL‐26 is involved in the production and promotion of malignant pleural effusion (MPE) for the first time. The concentrations of IL‐26 and several Th17‐related cytokines in MPE and peripheral blood (PB) from MPE patients were measured. IL‐26, IL‐10, and IL‐6 were elevated in MPE compared to PB. The cell resource of IL‐26 was primary Th17 cells measured by flow cytometry, whereas Tc17 cells and macrophages could also contribute to higher concentration of IL‐26 in MPE. Abundant IL‐6 and IL‐23 in MPE could promote the frequency of IL‐26 expressed by CD4+ T cells through phosphorylating STAT3 signaling pathway and promoting the expression of a specific Th17 lineage marker RORγt subsequently. IL‐26 could selectively increase Th22 proportion through up‐regulating the percentage of Ki‐67 expressed by CD4+ T cells and the expression of IL‐22 secreted by memory CD4+ T cells. In addition, IL‐26 could decrease secretion of granzyme B. The tumor‐killing activity of CD8+ T cells were inhibited as well when cocultured with malignant cells. Furthermore, the accumulation of IL‐26 protein in MPE predicted poor patient survival. In summary, our results indicated that IL‐26 was involved in the pathogenesis of MPE by exerting its impacts on both CD4+ T cells and CD8+ T cells. Graphical IL‐26 appears to be a vital effector cytokine that contributes to the pathogenesis of malignant pleural effusion (MPE), and could be a prognostic indicator for MPE.