The Regulation between CD4(+)CXCR5(+) Follicular Helper T (Tfh) Cells and CD19(+)CD24(hi)CD38(hi) Regulatory B (Breg) Cells in Gastric Cancer

Purpose. T follicular helper (Tfh) cells and regulatory B (Breg) cells are reported to play essential roles in humoral immunity, especially in inflammation, autoimmune diseases, and cancer. Hence, we sought to investigate the involvement of CXCR5(+)CD4(+) Tfh cells and CD19(+)CD24(hi)CD38(hi) Breg cells in gastric cancer. Methods. The blood samples were obtained from 36 gastric cancer patients and 18 healthy individuals. The percentage of Tfh cells (Tfh%) and Breg cells (Breg%) was detected via flow cytometry, while IL-21, IL-10, and CXCL13 levels were examined with ELISA. The association between them and clinical parameters of patients was also assessed. The in vitro Tfh-B cell coculture experiments were performed for six days, and then, Tfh%, Breg%, and cytokines were valued by flow cytometry and ELISA, respectively. Results. Tfh%, Breg%, and CXCL13 level were significantly increased among gastric cancer patients. Moreover, higher Tfh% was associated with lymphatic metastasis, patients' worse outcomes and Breg%. Tfh differentiation and CXCL13 were upregulated by cocultured B cells in vitro, while Tfh cells seem to not participate in Breg cell differentiation from B cells. Conclusion. Altogether, increased Tfh and Breg cells could be involved in immune suppression in gastric cancer. Moreover, B cell may be a potential regulator for Tfh differentiation, while Tfh cells had no significant effects on the regulation of Breg cells.

Automated summary

This study investigated the involvement of CXCR5(+)CD4(+) T follicular helper (Tfh) cells and CD19(+)CD24(hi)CD38(hi) regulatory B (Breg) cells in gastric cancer. The results showed that Tfh cells, Breg cells, and CXCL13 levels were significantly increased in gastric cancer patients. Higher levels of Tfh cells were associated with lymphatic metastasis, worse patient outcomes, and increased Breg cells. In vitro coculture experiments demonstrated that B cells could promote Tfh differentiation and CXCL13 expression, while Tfh cells had no significant effect on Breg cell regulation.