IL-17A-producing T cells and associated cytokines are involved in the progression of gastric cancer

Abstract

Interleukin-17A-producing T cells (IL-17A+ T) (IL-17A+CD4+ Th17, IL-17A+CD8+ Tc17 and IL-17A+ γδT17 cells) and associated cytokines (IL-17A, IL-23 and IL-1β) play crucial roles in inflammation-associated diseases, such as infection, autoimmunity and tumors. Th17 cells promote human gastric cancer (GC), although the source of intracellular IL‑17A and the roles of Tc17 and γδT17 cells remain poorly understood. In this study, the frequencies of circulating Th17 and γδT17 cells in patients with GC were found to be significantly increased compared to those in healthy donors; however, Tc17 cells were decreased in these patients, and a negative relationship was found between the frequencies of Th17 and Tc17 cells. Moreover, the cytokine IL‑17A was found to be produced mainly by Th17 cells in human peripheral blood. Similarly, serum cytokine levels and relative mRNA expression levels of IL‑17A, IL‑23 and IL‑1β were significantly increased in patients with GC, and the frequency of Th17 cells was closely associated with serum IL‑17A concentrations in patients with GC. Additionally, Th17 cells and associated cytokines were present at significantly different levels during the progression and metastasis of GC, as were Tc17 and γδT17 cells. Taken together, these findings suggest that IL-17A+ T cells and associated cytokines might play crucial roles in human GC progression and metastasis and thus represent potential targets for treatment.

Treatment to sustain a Th17‐type phenotype to prevent skewing toward Treg and to limit premalignant lesion progression to cancer

“…The role of Th17 cells in cancer development has been conflicting and may depend on whether the role is being evaluated in the context of inflammation‐induced tumor promotion or their role in later stages of tumor progression. Assessments of Th17 and IL‐17 levels in the peripheral blood of gastric cancer patients showed levels to be increased as compared to levels in healthy controls . Also, expression of Th17‐associated cytokines in patients with hypopharyngeal carcinoma was increased with more advanced‐stage cancer .…”

“…Assessments of Th17 and IL-17 levels in the peripheral blood of gastric cancer patients showed levels to be increased as compared to levels in healthy controls. 16 Also, expression of Th17-associated cytokines in patients with hypopharyngeal carcinoma was increased with more advanced-stage cancer. 15 In contrast, while IL-17 and other Th17-associated cytokine levels were elevated in non-small cell lung cancer patients, Figure 8.…”

“…Several studies have shown correlations between cancer presence and increased levels of Th17 cells or Th17 cell‐associated cytokines, raising suggestions that the Th17 cells contribute to the tumor development and progression. This includes increased levels of Th17 cells or IL‐17 in patients with cervical cancer, hypopharyngeal carcinoma, gastric cancer and lung cancer . The contribution of Th17 cells to inflammation, such as in the gut, has been implicated in the development of colon cancer .…”

“…This includes increased levels of Th17 cells or IL-17 in patients with cervical cancer, hypopharyngeal carcinoma, gastric cancer and lung cancer. [14][15][16][17] The contribution of Th17 cells to inflammation, such as in the gut, has been implicated in the development of colon cancer. 18 In addition to studies showing associations between the presence of Th17 cells and cancer, a few interventional studies have been conducted, although results of some of these studies are conflicting.…”

Neuroimmune Alterations in Autism: A Translational Analysis Focusing on the Animal Model of Autism Induced by Prenatal Exposure to Valproic Acid

“…IL-17-producing cells, including NK cells and innate lymphoid cells, play crucial roles in inflammation-associated disease, such as infection, autoimmunity, and tumors [139]. The effector role of IL-17a at the onset of MIA-induced behavioral abnormalities in offspring has also been described, showing the important crosstalk between the neuroinflammatory state and behavioral manifestations [140].…”