期刊
INTERNATIONAL JOURNAL OF CANCER
卷 129, 期 10, 页码 2417-2426出版社
WILEY-BLACKWELL
DOI: 10.1002/ijc.25902
关键词
CD103; regulatory T cell; FoxP3; tumor
类别
资金
- LMU
- Friedrich Baur Foundation
- German Research Foundation [Graduiertenkolleg 1202]
- Deutsche Krebshilfe
- BayImmuNet [CIPS-M 114]
Regulatory T cells (Treg) mediate tolerance towards self-antigens by suppression of innate and adaptive immunity. In cancer patients, tumor-infiltrating FoxP3+ Treg suppress local anti-tumor immune responses and are often associated with poor prognosis. Markers that are selectively expressed on tumor-infiltrating Treg may serve as targets for immunotherapy of cancer. Here we show that CD103, an integrin mediating lymphocyte retention in epithelial tissues, is expressed at high levels on tumor-infiltrating FoxP3+ Treg in several types of murine cancer. In the CT26 model of colon cancer up to 90% of the intratumoral FoxP3+ cells expressed CD103 compared to less than 20% in lymphoid organs. CD103+ Treg suppressed T effector cell activation more strongly than CD103(neg) Treg. Expression of CD103 on Treg closely correlated with intratumoral levels of transforming growth factor beta (TGF-beta) and could be induced in a TGF-beta-dependent manner by tumor cell lines. In vivo, gene silencing of TGF-beta reduced the frequency of CD103+ Treg, demonstrating that CD103 expression on tumor-infiltrating Treg is driven by intratumoral TGF-beta. Functional blockade of CD103 using a monoclonal antibody did however not reduce the number of intratumoral Treg, indicating that CD103 is not involved in homing or retention of FoxP3+ cells in the tumor tissue. In conclusion, expression of CD103 is a hallmark of Treg that infiltrate TGF-beta-secreting tumors. CD103 thus represents an interesting target for selective depletion of tumor-infiltrating Treg, a strategy that may help to improve anti-cancer therapy.
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