Proinflammatory follicular helper T cells promote immunoglobulin G secretion, suppress regulatory B cell development, and correlate with worse clinical outcomes in gastric cancer

Abstract

Gastric cancer is one of the most common and aggressive malignancies. Both bacterial virulence factors and host chronic inflammation are thought to promote gastric cancer development. In this study, we investigated the potential involvement of follicular helper T cells in gastric cancer. Functions of follicular helper T subsets were examined in Helicobacter pylori-infected gastric cancer patients and H. pylori-infected but asymptomatic individuals. We found that the follicular helper T cells in gastric cancer individuals were skewed toward the Th1 and Th17 subsets compared to those in H. pylori-infected but asymptomatic individuals. In a naive B cell-follicular helper T cell coculture, the Th1-follicular helper T cells by themselves were ineffective at stimulating a robust antibody response, unlike the Th2-follicular helper T and Th17-follicular helper T cells. However, Th1-follicular helper T cells significantly promoted the immunoglobulin G response in collaboration with other follicular helper T subsets, through the secretion of interferon gamma. We also found that Th1-follicular helper T cells suppressed the development of interleukin-10 regulatory B cells, a cell type previously thought to protect H. pylori-infected individuals from tissue damage. In addition, the frequency of Th1-follicular helper T cells in gastric cancer patients was negatively correlated with the disease-free survival of gastric cancer patients after tumor resection. These results suggested that dysregulation of follicular helper T subsets in gastric cancer patients, characterized by increased Th1-follicular helper T cells, contributed to inflammation and tumor development.

Functionally impaired follicular helper T cells induce regulatory B cells and CD14+ human leukocyte antigen‐DR− cell differentiation in non‐small cell lung cancer

“…Here, we found decreased IL‐21 levels and a negative correlation between IL‐21 and Tfh and Tfh17 cells, indicating that IL‐21 production of Tfh17 cells could be greatly impaired in NSCLC. GC and circulating Tfh cells can stimulate the production of antibodies through the expression of IL‐10 and IL‐21 . Ma reported that Tfh cells from NSCLC patients were defective at helping naive B cells induce IgM, IgG, and IgA production.…”

Upregulation of ZHX2 predicts poor prognosis and is correlated with immune infiltration in gastric cancer

“…Finally, to further confirm the relationship between ZHX2 and immune infiltrating cells, we analyzed the connection between ZHX2 and marker genes of immune infiltration cells and revealed that ZHX2 was also positively correlated with the marker genes of T helper cells (Th1, Th2, Tfh, Th17 and Tregs) and dendritic cells. Th1 [24], Th2 [25] and Th17 [26] in GC also predicted poor prognosis, and these results indicated that ZHX2 might regulate the T cell function to affect tumorigenesis in GC.…”

The Progress of T Cell Immunity Related to Prognosis in Gastric Cancer

“…Zhang et al investigated the potential functions of Follicular helper T cells in the GCs with Helicobacter pylori infection. His group found that Th1 and Th17 are the most common subsets of Follicular helper T cells and can be negatively correlated with the disease-free survival of tumor resection [ 45 ].…”