Department of Gastroenterology Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Surg Oncol. 2011 Nov 1;104(6):571-7. doi: 10.1002/jso.22005. Epub 2011 Jun 21.
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.
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.
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.
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.
调节性 T 细胞（Treg）抑制 T 细胞介导的免疫反应。本研究旨在探讨 Treg 是否在人类胃癌组织中积聚，以及胃癌细胞诱导 Treg 的机制。
对胃腺癌组织浸润的白细胞进行流式细胞术和免疫组织化学分析。分析 Treg 的比例、表型、功能和临床相关性。通过 Western blot 测定癌细胞产生的 TGF-β1，并进行体外共培养实验模拟胃癌微环境。
胃癌组织中 CD4(+) Foxp3(+) T 细胞的比例明显高于相邻非肿瘤胃组织（P<0.05）。经典 Treg 表型和增殖实验的结果支持升高的 CD4(+) Foxp3(+) T 细胞代表一种具有抑制功能的 Treg 群体。高比例的 Treg 与进展期 TNM 分期和生存率降低相关。原发性胃癌细胞产生大量 TGF-β1，负责 Treg 的转化。
功能性 Treg 在人类胃癌中的比例升高，与预后不良相关。胃癌细胞通过 TGF-β1直接将 CD4(+) naive T 细胞转化为 Treg，提示肿瘤细胞逃避免疫系统的一种可能机制。
