title: Increased intratumoral IL-22-producing CD4(+) T cells and Th22 cells correlate with gastric cancer progression and predict poor patient survival.
abstract: IL-22-producing CD4(+) T cells (IL-22(+)CD4(+) T cells) and Th22 cells (IL-22(+)IL-17(-)IFN-γ(-)CD4(+) T cells) represent newly discovered T-cell subsets, but their nature, regulation, and clinical relevance in gastric cancer (GC) are presently unknown. In our study, the frequency of IL-22(+)CD4(+) T cells in tumor tissues from 76 GC patients was significantly higher than that in tumor-draining lymph nodes, non-tumor, and peritumoral tissues. Most intratumoral IL-22(+)CD4(+) T cells co-expressed IL-17 and IFN-γ and showed a memory phenotype. Locally enriched IL-22(+)CD4(+) T cells positively correlated with increased CD14(+) monocytes and IL-6 and IL-23 detection ex vivo, and in vitro IL-6 and IL-23 induced the polarization of IL-22(+)CD4(+) T cells in a dose-dependent manner and the polarized IL-22(+)CD4(+) T cells co-expressed of IL-17 and IFN-γ. Moreover, IL-22(+)CD4(+) T-cell subsets (IL-22(+)IL-17(+)CD4(+), IL-22(+)IL-17(-)CD4(+), IL-22(+)IFN-γ(+)CD4(+), IL-22(+)IFN-γ(-)CD4(+), and IL-22(+)IL-17(+)IFN-γ(+)CD4(+) T cells), and Th22 cells were also increased in tumors. Furthermore, higher intratumoral IL-22(+)CD4(+) T-cell percentage and Th22-cell percentage were found in patients with tumor-node-metastasis stage advanced and predicted reduced overall survival. In conclusion, our data indicate that IL-22(+)CD4(+) T cells and Th22 cells are likely important in establishing the tumor microenvironment for GC; increased intratumoral IL-22(+)CD4(+) T cells and Th22 cells are associated with tumor progression and predict poorer patient survival, suggesting that tumor-infiltrating IL-22(+)CD4(+) T cells and Th22 cells may be suitable therapeutic targets in patients with GC.
authors.affiliation: Department of Clinical Microbiology and Immunology, College of Medical Laboratory Science, Third Military Medical University, No.30 Gaotanyan street, Chongqing, 400038, People's Republic of China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhuang
authors.forename: Liu-Sheng
authors.initials: LS
authors.lastname: Peng
authors.forename: Yong-Liang
authors.initials: YL
authors.lastname: Zhao
authors.forename: Yun
authors.initials: Y
authors.lastname: Shi
authors.forename: Xu-Hu
authors.initials: XH
authors.lastname: Mao
authors.forename: Gang
authors.initials: G
authors.lastname: Guo
authors.forename: Weisan
authors.initials: W
authors.lastname: Chen
authors.forename: Xiao-Fei
authors.initials: XF
authors.lastname: Liu
authors.forename: Jin-Yu
authors.initials: JY
authors.lastname: Zhang
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Luo
authors.forename: Pei-Wu
authors.initials: PW
authors.lastname: Yu
authors.forename: Quan-Ming
authors.initials: QM
authors.lastname: Zou
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016764:Cell Polarity / Q000276:immunology; D002478:Cells, Cultured; D018920:Coculture Techniques; D018450:Disease Progression; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007378:Interleukins / Q000276:immunology*; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology; D013274:Stomach Neoplasms / Q000276:immunology* / Q000401:mortality; D000097043:Interleukin-22
chemical_list: D007371:Interferon-gamma; D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6; D007378:Interleukins; D018950:Lipopolysaccharide Receptors; D000097043:Interleukin-22; C508600:IL6 protein, human