<p>Effect of Th9/IL-9 on the growth of gastric cancer in nude mice</p>

Abstract

Objective By neutralizing IL-9 in a nude mouse model, the study aimed to investigate the role of Th9/IL-9 on the growth of gastric cancer in mice. Materials and methods Male BALB/c nude mice were randomly divided into three groups: a normal control group (Control), an SGC-7901 xenografted nude mice model group (Model), and a rIL-9 treatment group (Treat). The weight of the tumors was recorded to calculate the tumor inhibition rate. Flow cytometry was used to detect the cell frequency of Th9, Th17, and Treg in peripheral blood. The IL-4, IL-9, IL-10, IL-25, VEGF, and TGF-β levels in serum were determined by ELISA. The cellular migration and invasion were investigated by transwell assay. Immunohistochemical and Western blot were used to detect the expression of IL-9, CD34, PU.1, p53, and p21 proteins in gastric cancer tissue. The mRNA expression levels of IL-9, IL-21, and PU.1 in gastric cancer tissue were determined by qRT-PCR. Result rIL-9 can significantly inhibit the growth of gastric cancer. The frequency of Th9, Th17, and Treg in peripheral blood was decreased upon treatment. The levels of IL-4, IL-9, IL-10, IL-25, VEGF, and TGF-β in serum were significantly reduced in the Treat group compared with the Model group ( P <0.05). rIL-9 can inhibit cellular migration and invasion and reduce the mRNA level of IL-9, IL-21, and PU.1. Meanwhile, in the Treat group, the expression of IL-9, CD34, and PU.1 was significantly reduced, whereas the expression of p53 and p21 was significantly increased compared with the Model group ( P <0.05). Conclusion This study suggested that Th9/IL-9 has a deleterious role in gastric cancer.

Deleterious Role of Th9 Cells in Pulmonary Fibrosis

“…Moretti et al found that IL-9 increased IL-2 production by mast cells, resulting in an expansion of CD25 + type 2 congenital lymphoid cells (ILC2) and subsequent activation of Th9 cells, suggesting that neutralizing IL-9 may reduce Th9 cell activation by blocking this pathway [39]. Cai et al also showed that neutralizing IL-9 reduced the proportion of Th9 cells in mice [50]. Consistent with these findings, we found that neutralizing IL-9 reduced the proportions of Th2 cells and Th9 cells in the lungs of mice.…”

IL-9 and IL-9-producing cells in tumor immunity

“…Researchers have found that the levels of IL-4, IL-10, VEGF and TGF-β are decreased in IL-9-treated tumor-bearing nude mice. Moreover, IL-9 can inhibit the proliferation and migration of the gastric cancer cell line SGC-7901 in vitro [57]. IL-9 also exerts a strong antitumor response in colon cancer, and the expression level of IL-9 in colon cancer is positively correlated with TNM stage, lymph node metastasis, and good prognosis.…”

“…This is contradictory to the result we aforementioned result and such contradictory result is common because breast cancer in human and mice may have different mechanisms, which need to be studied further. Moreover, Th9 cells and Th9 cell-derived IL-9 also have a strong ability to inhibit tumor metastasis and growth in metastatic lung cancer and gastric cancer in nude mice [57,70]. Th9 cells can also kill tumor cells directly by secreting granzyme B in some tumors [32].…”

TGF-β and Cancer Immunotherapy

“…On the other hands, IL-9-treatment in SGC-7901 (Gastric tumor cell line) xenografted nude mice showed less tumor growth. 29) Another report has been shown that Th9 cells induce anti-tumor immunity via enhancement of IFN-γ production from CD8 + T cells and natural killer (NK) cells. 30) Recently, Li et al generated 4T-Trap, anti-human CD4 antibody with TGF-βRII extra cellular domain, which is selectively blockade of TGF-β signaling in CD4 + T cells and promotes cancer immunotherapy.…”