Th22 Cells/IL-22 Serves as a Protumor Regulator to Drive Poor Prognosis through the JAK-STAT3/MAPK/AKT Signaling Pathway in Non-Small-Cell Lung Cancer

Abstract

The interaction of immune cells and cytokines in the tumor microenvironment affects the development and prognosis of tumors with an unclear potential regulatory mechanism. Recent studies have elucidated the protumor role of Th22 cells and its lineage-specific cytokine IL-22 in different human cancers. The present study is aimed at investigating the biological effect of Th22 cells/IL-22 and its molecular mechanism in the pathogenesis process of non-small-cell lung cancer (NSCLC). It was initially found that Th22 cells were enriched in the peripheral blood of NSCLC patients. The level of Th22 cells in peripheral blood mononuclear cells (PBMCs) was positively correlated with the TNM stage, lymph node metastasis, and clinical tumor biomarkers. Furthermore, IL-22 not only antagonized the apoptosis inducing and cell cycle arresting effect by chemotherapy and molecular targeted drugs on NSCLC cell lines but also promoted tumor cell proliferation and tumor tissue growth. Moreover, IL-22 activated the JAK-STAT3/MAPK/AKT signaling pathway, both in vitro and in vivo. Conclusively, the present results confirm that Th22 cells/IL-22 may serve as a negative immune regulator in lung cancer.

Shenqi Fuzheng injection restores the sensitivity to gefitinib in non-small cell lung cancer by inhibiting the IL-22/STAT3/AKT pathway

“… 2021 ; Yao et al. 2022 ). To investigate whether IL-22 is involved in signal transduction in gefitinib-resistant PC9/GR and H1975 cells, we stimulated these NSCLC cells with exogenously added IL-22, at a 50 ng/mL concentration and measured the p-STAT3 and p-AKT protein levels 10 and 30 min after stimulation.…”

Electroacupuncture improves apoptosis of nucleus pulposus cells via the IL-22/JAK2-STAT3 signaling pathway in a rat model of cervical intervertebral disk degeneration

“…Previous studies have demonstrated that the IL-22/ JAK2-STAT3 signaling pathway is activated in the progression of multiple diseases. 21,35 STAT3 functions as a key signal transduction molecule in many inflammatory diseases. 36 Suzuki et al 37 and Chen et al 38 confirmed that the JAK2-STAT3 pathway was activated in a rat model of IVD degeneration and STAT3 was highly expressed in the IVD tissue, similar to our results.…”

“…18,19 In recent studies, IL-22 was found to activate the JAK2-STAT3 signaling pathway both in vitro and in vivo. 20,21 However, to our knowledge, no study has focused on the IL-22/JAK2-STAT3 signaling pathway in IVD degeneration.…”

Role and Potential of Different T Helper Cell Subsets in Adoptive Cell Therapy

“…So far, Th22 cells and their main signature, cytokine IL-22, have been associated with tumor progression in patients with hepatocellular carcinoma [ 148 ], colon cancer [ 149 ], lung cancer [ 150 , 151 ], gastric cancer [ 152 ], and ovarian cancer [ 153 ], among others. This is probably due to the effect of IL-22, which has been shown to inhibit apoptosis and promote tumor cell proliferation, angiogenesis, migration, epithelial-to-mesenchymal transition, and metastasis [ 148 , 151 , 154 , 155 , 156 , 157 , 158 ].…”