Accumulation of T‑helper 22 cells, interleukin‑22 and myeloid‑derived suppressor cells promotes gastric cancer progression in elderly patients

Abstract

Chronic inflammation and immunosuppression lead to aging and tumorigenesis. T-helper 22 (Th22) cells, interleukin 22 (IL-22) and myeloid-derived suppressor cells (MDSCs) serve an important role in inflammatory-immune diseases and cancer. However, the status of Th22 cells, IL-22 and MDSCs in aging and elderly gastric cancer progression is unknown. In the present study, 39 elderly patients with gastric cancer (EGC), 32 elderly healthy controls (HE) and 31 young healthy controls (HY) were enrolled, and the peripheral Th22, Th17 and Th1 cells, and MDSCs, were examined using flow cytometry. Plasma levels of IL-22, IL-6 and tumor necrosis factor-α (TNF-α) were examined using ELISA. IL-22 protein levels in tumor tissues were examined using immunohistochemistry. There were increased numbers of peripheral Th22 and Th17 cells, and MDSCs, as well as increased plasma levels of IL-22, IL-6 and TNF-α in EGC compared with HE and HY. However, HE exhibited significantly increased levels of peripheral Th22 and Th17 cells as well as IL-6 and TNF-α compared with HY. Immunohistochemical analysis demonstrated that IL-22 protein accumulated in tumor cells and lymphocytes in the tumor microenvironment. The results obtained demonstrated that peripheral Th22 and Th17 cells as well as IL-6 and TNF-α plasma levels increased with aging. Furthermore, Th22 and Th17 cells, MDSCs, and IL-22 may be used as prognostic markers for identifying gastric cancer in elderly patients.

Impact of Immunotherapy on CD4 T Cell Phenotypes and Function in Cancer

“…Moreover, Amicarella et al showed this dual role of Th17 cells in CRC, where CRC-derived Th17 cells triggered the release of protumorigenic factors by the tumor, while favoring the recruitment of beneficial neutrophils [ 21 ]. Th22 cells also promote tumorigenesis in some cancers such as colon [ 22 ] and gastric cancer [ 23 ]. Indeed, it was shown that Th22 cells increased as tumor stage advanced and their frequency was predictive of reduced overall survival.…”

A Double Edged Sword Role of Interleukin-22 in Wound Healing and Tissue Regeneration

“…IL-22 has been revealed to act as a pro-tumor cytokine in the cancers associated with gastrointestinal tract. The infiltration of cellular sources of IL-22 including Th22 and CD4+ T cells in the intratumoral tissue increases, corresponding to the stage of tumor (153)(154)(155). Patients with gastric tumors have also been shown to have increased levels of circulating T cells secreting IL-22 as well as IL-17, thus showing a positive association with tumor progression (154).…”

TH9, TH17, and TH22 Cell Subsets and Their Main Cytokine Products in the Pathogenesis of Colorectal Cancer

“…Regarding the role of T H 22/IL-22 in cancers, evidence from early studies revealed that IL-22 promotes the growth of tumor cells in many types of cancers, including lung adenocarcinoma and hepatocellular carcinoma (128, 129). In patients with gastric cancer, dysregulation of circulating T H 22 cell frequency and IL-22 expression levels have been demonstrated, and were associated with advanced tumor features and patient survival (130, 131). Regarding the role of T H 22/IL-22 in CRC, in vitro studies have shown that IL-22 enhances nitric oxide synthase expression in colon cancer cells, significantly contributing to conversion to nitrites, which are associated with colonic inflammation and carcinogenesis (132).…”