期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 45, 期 6, 页码 1654-1666出版社
WILEY
DOI: 10.1002/eji.201445058
关键词
Colorectal cancer; CXCL9; CXCL10; Treg cell
类别
资金
- Swedish Science Council
- Swedish Cancer Foundation
- Sahlgrenska University Hospital
- Ruth and Richard Julin foundation
- Assar Gabrielssons foundation
- Olle Engkvist's foundation
- Hvitfeldska foundation
Colorectal cancer (CRC) is one of the most prevalent tumor types worldwide and tumor-infiltrating T cells are crucial for anti-tumor immunity. We previously demonstrated that Treg cells from CRC patients inhibit transendothelial migration of conventional T cells. However, it remains unclear if local Treg cells affect lymphocyte migration into colonic tumors. By breeding APC(Min/+) mice with depletion of regulatory T cells mice, expressing the diphtheria toxin receptor under the control of the FoxP3 promoter, we were able to selectively deplete Treg cells in tumor-bearing mice, and investigate the impact of these cells on the infiltration of conventional T cells into intestinal tumors. Short-term Treg-cell depletion led to a substantial increase in the frequencies of T cells in the tumors, attributed by both increased infiltration and proliferation of T cells in the Treg-cell-depleted tumors. We also demonstrate a selective increase of the chemokines CXCL9 and CXCL10 in Treg-cell-depleted tumors, which were accompanied by accumulation of CXCR3(+) T cells, and increased IFN- mRNA expression. In conclusion, Treg-cell depletion increases the accumulation of conventional T cells in intestinal tumors, and targeting Treg cells could be a possible anti-tumor immunotherapy, which not only affects T-cell effector functions, but also their recruitment to tumors.
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