Activated but not resting regulatory T cells accumulated in tumor microenvironment and correlated with tumor progression in patients with colorectal cancer.
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.
Department of Hematology-Oncology, Linkou Medical Center, Chang Gung Memorial Hospital, Kweishan, Tayouan, Taiwan.
Yung-Chang
YC
Lin
Jayashri
J
Mahalingam
Jy-Ming
JM
Chiang
Po-Jung
PJ
Su
Yu-Yi
YY
Chu
Hsin-Yi
HY
Lai
Jian-He
JH
Fang
Ching-Tai
CT
Huang
Cheng-Tang
CT
Chiu
Chun-Yen
CY
Lin
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060908:CTLA-4 Antigen / Q000032:analysis; D015179:Colorectal Neoplasms / Q000276:immunology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007156:Immunologic Memory; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008875:Middle Aged; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D059016:Tumor Microenvironment
D060908:CTLA-4 Antigen; D047889:Receptors, Tumor Necrosis Factor, Type II; D017493:Leukocyte Common Antigens