Prevalence of Th17 and Treg cells in gastric cancer patients and its correlation with clinical parameters

Abstract

Th17 cells and CD4+CD25+ regulatory T (Treg) cells have been reported to share reciprocal developmental pathways but exhibit opposite effects, and the balance between them controls inflammation and autoimmune diseases. However, information regarding Th17/Treg cells in cancer-bearing hosts is still limited. In the present study, we investigated the distribution of Th17 cells in relation to Treg cells in gastric cancer patients, and evaluated how the imbalance in Th17/Treg cells in gastric cancer correlates with clinical and pathological parameters. We observed that the accumulation of Th17 and Treg cells in the tumor microenvironment was gradually increased according to disease progression, leading to an imbalance in Th17/Treg cells in gastric cancer patients. TGF-β and interleukin (IL)‑6 present in the gastric cancer microenvironment promoted the differentiation and expansion of Th17 cells, and increased numbers of Th17 cells promoted tumor progression through promotion of inflammation by secretion of IL-17. Treg cells promoted tumor progression by helping cancer cells escape from host immunosurveillance by secreting TGF-β, and a high level of TGF-β in the tumor microenvironment promoted differentiation and expansion of Treg cells. In conclusion, the imbalance in Th17/Treg cells was involved in the development and progression of gastric cancer. A better understanding of the nature, regulation, and function of Th17 and Treg cells in tumor immunity may aid in the development of novel and effective immunotherapy for gastric cancer.

Tumor infiltration by Tbet+ effector T cells and CD20+ B cells is associated with survival in gastric cancer patients

“…28 Even if gastric cancer is frequently associated with Helicobacter pylori-induced gastritis, a high density of Foxp3 C cells is usually associated with a poor prognosis, as found in our present study and predominating the literature. [29][30][31][32] Only Haas et al found a relationship between high levels of Foxp3C cell tumor infiltration and improved prognosis in 52 patients bearing gastric adenocarcinomas of the cardia. 33 In the present work, we did not find a significant correlation between gastric cancer patient survival and the density of CD8 C or IL-17 C tumor-infiltrating cells.…”

Expression of Th17/Treg related molecules in gastric cancer tissues

“…Th17 and Treg may both exhibit ascending trend with TNM stage, or Treg rather than Th17 increases in advanced gastric cancer (10,31). There are also differences between the distribution of Th17 and Treg in peripheral blood and cancer tissues.…”

“…The expression of Th17 and Treg in the diseases is related to the factors that influence their differentiation (20,21). Moreover, the function of Th17 and Treg in the diseases depends on the effectors that are synthesized and secreted by them (10,11). The correlation between the factors that induce their differentiation and their effect factors in the disease has not been reported systematically.…”

“…As major components of the adaptive immune system, Th17 as well as Treg are not only involved in the maintenance or inhibition of chronic inflammation, but also play important roles in various cancers, such as lung cancer, endometrial carcinoma, colorectal cancer, as well as gastric cancer (5)(6)(7)(8)(9)(10). In our recent report, IL-17, mainly produced by Th17, may be the important promoting factor in the development and progress of gastric cancer and angiogenesis may be one of the underlying mechanisms (11).…”

“…TGF-β1 alone promoted the generation of Treg through the induction of the transcription factor defined as forkhead box protein 3 (FoxP3), while CD4+ T cells will differentiate into Th17 by the combined action of IL-6 and TGF-β1 through orphan nuclear receptor (ROR) γt, signal transducer, and activator of transcription (STAT3) (12,13). Subsequently, the imbalance of Th17/Treg in gastric cancer has been focused on (10). However, the regulating mechanisms are still unknown.…”