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Activated but not resting regulatory T cells accumulated in tumor microenvironment and correlated with tumor progression in patients with colorectal cancer
Author(s) -
Lin YungChang,
Mahalingam Jayashri,
Chiang JyMing,
Su PoJung,
Chu YuYi,
Lai HsinYi,
Fang JianHe,
Huang ChingTai,
Chiu ChengTang,
Lin ChunYen
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27784
Subject(s) - foxp3 , cytotoxic t cell , tumor necrosis factor alpha , il 2 receptor , colorectal cancer , tumor microenvironment , immune system , t cell , cytokine , cancer research , cancer , medicine , biology , immunology , in vitro , biochemistry
Activated T regulatory (T reg ) cells are potent suppressors that mediate immune tolerance. We investigated the relationship between activated T reg 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 T reg cells with colon cancer stage. The phenotypes, cytokine‐release patterns and suppression ability of these T reg cells were analyzed. We found that T reg cells increased significantly in both peripheral blood and cancer tissue. In addition, the T reg cells expressed significantly lower levels of CCR7, CD62L and CD45RA in comparison to normal volunteers. Further dividing T reg cells into subgroups based on Foxp3 and CD45RA expression revealed that both activated T reg cells (Foxp3 hi CD45RA − ) and nonsuppressive T reg cells (Foxp3 lo CD45RA − ), but not resting T reg cells (Foxp3 low CD45RA + ), increased in the peripheral blood and cancer tissue of patients with colon cancer. Only the activated T reg cells expressed significantly higher levels of tumor necrosis factor receptor 2 and cytotoxic T‐cell antigen‐4. Activated T reg cells, however, secreted significantly lower levels of effector cytokines (interleukin‐2, tumor necrosis factor‐α and interferon‐γ) than did resting T reg cells and nonsuppressive cells upon ex vivo stimulation. Activated, but not resting, T reg cells in cancer tissue correlated with tumor metastases. In summary, we confirmed that activated T reg cells are a distinct subgroup with effector memory phenotype and fully functional regulatory activity against human colorectal cancer immunity.