Activated but not resting regulatory T cells accumulated in tumor microenvironment and correlated with tumor progression in patients with colorectal cancer

被引：91

作者：

Lin, Yung-Chang ^{[1
,2
]}

Mahalingam, Jayashri ^{[2
,3
]}

Chiang, Jy-Ming ^{[2
,4
]}

Su, Po-Jung ^{[1
]}

Chu, Yu-Yi ^{[1
]}

Lai, Hsin-Yi ^{[3
]}

Fang, Jian-He ^{[3
]}

Huang, Ching-Tai ^{[2
,5
]}

Chiu, Cheng-Tang ^{[2
,3
]}

Lin, Chun-Yen ^{[2
,3
]}

机构：

[1] Chang Gung Mem Hosp, Dept Hematol Oncol, Linkou Med Ctr, Kweishan, Tayouan, Taiwan

[2] Chang Gung Univ, Coll Med, Tao Yuan, Taiwan

[3] Chang Gung Mem Hosp, Dept Gastroenterol Hepatol, Linkou Med Ctr, Kweishan, Tayouan, Taiwan

[4] Chang Gung Mem Hosp, Colorectal Surg Sect, Linkou Med Ctr, Dept Surg, Kweishan, Tayouan, Taiwan

[5] Chang Gung Mem Hosp, Dept Infect Dis, Linkou Med Ctr, Kweishan, Tayouan, Taiwan

来源：

INTERNATIONAL JOURNAL OF CANCER | 2013年 / 132卷 / 06期

关键词：

colorectal cancer; regulatory T cell; effector memory T cells; tumor infiltrating lymphocyte; TRANSCRIPTION FACTOR FOXP3; VERSUS-HOST-DISEASE; LUNG-CANCER; IMMUNE-RESPONSES; BREAST-CANCER; IN-VIVO; EXPRESSION; IMMUNOTHERAPY; EFFECTOR/MEMORY; CARCINOMA;

D O I：

10.1002/ijc.27784

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

Activated T regulatory (Treg) cells are potent suppressors that mediate immune tolerance. We investigated the relationship between activated Treg cells and the progression of human colon cancer. We designed a cross-sectional study of CD4+Foxp3+ T cells from peripheral blood, primary tumor and nontumor colon tissue of 42 patients with colon cancer and correlated the percentages of different subgroups of Treg cells with colon cancer stage. The phenotypes, cytokine-release patterns and suppression ability of these Treg cells were analyzed. We found that Treg cells increased significantly in both peripheral blood and cancer tissue. In addition, the Treg cells expressed significantly lower levels of CCR7, CD62L and CD45RA in comparison to normal volunteers. Further dividing Treg cells into subgroups based on Foxp3 and CD45RA expression revealed that both activated Treg cells (Foxp3hiCD45RA-) and nonsuppressive Treg cells (Foxp3loCD45RA-), but not resting Treg cells (Foxp3lowCD45RA+), increased in the peripheral blood and cancer tissue of patients with colon cancer. Only the activated Treg cells expressed significantly higher levels of tumor necrosis factor receptor 2 and cytotoxic T-cell antigen-4. Activated Treg cells, however, secreted significantly lower levels of effector cytokines (interleukin-2, tumor necrosis factor-a and interferon-?) than did resting Treg cells and nonsuppressive cells upon ex vivo stimulation. Activated, but not resting, Treg cells in cancer tissue correlated with tumor metastases. In summary, we confirmed that activated Treg cells are a distinct subgroup with effector memory phenotype and fully functional regulatory activity against human colorectal cancer immunity.

引用

页码：1341 / 1350

页数：10

共 50 条

[1]

Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production [J].