CD103 is a hallmark of tumor‐infiltrating regulatory T cells

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 CD103neg Treg. Expression of CD103 on Treg closely correlated with intratumoral levels of transforming growth factor β (TGF‐β) and could be induced in a TGF‐β‐dependent manner by tumor cell lines. In vivo, gene silencing of TGF‐β reduced the frequency of CD103+ Treg, demonstrating that CD103 expression on tumor‐infiltrating Treg is driven by intratumoral TGF‐β. 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‐β‐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.