Conversion of intratumoral regulatory T cells by human gastric cancer cells is dependent on transforming growth factor-β1.

Background And Objectives: Regulatory T cells (Treg) inhibits immune responses mediated by T cells. This study aimed to investigate whether Treg are accumulated in human gastric cancer tissue and the mechanism of Treg induction by gastric cancer cells.

Methods: Tissue infiltrated leukocytes from gastric adenocarcinomas were subjected to flow cytometry and immunohistochemistry. Percentage, phenotype, function, and clinical relevance of Treg were analyzed. TGF-β1 production by cancer cells was determined by Western blot and in vitro co-culture experiments were performed to mimic gastric cancer microenvironment.

Results: The percentages of CD4(+) Foxp3(+) T cells in gastric cancer tissues were significantly higher than those from adjacent non-tumor gastric tissues (P < 0.05). The results of classical Treg phenotype and proliferation assay supported that the elevated CD4(+) Foxp3(+) T cells represents a suppressive Treg population. High proportion of Treg is correlated to advance TNM stage and reduced survival. Primary gastric cancer cells produced abundance of TGF-β1 which was responsible for conversion of Treg.

Conclusion: The proportion of functional Treg is elevated in human gastric cancer and related to poor prognosis. Gastric cancer cells directly convert CD4(+) naive T cells to Treg by TGF-β1, suggesting a possible mechanism through which tumor cells evade the immune system.