Increased intratumoral IL-22-producing CD4+ T cells and Th22 cells correlate with gastric cancer progression and predict poor patient survival
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.
KeywordsGastric cancer IL-22+CD4+ T cells Th22 cells Tumor progression Tumor survival
This work was supported by grants of the National Natural Science Foundation of China (NSFC, No. 81071412), and National Basic Research Program of China (973 program, No. 2009CB522606).
Conflict of interest
The authors declare that they have no conflict of interest.
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