Regulatory T cells (Treg) are critical mediators of self-tolerance but can also limit effective anti-tumor immunity. We and others previously reported that 40-60% percent of Treg-infiltrating head and neck cancer (HNC) and other tumors highly express Tim-3, compared with about 5% in lymphoid organs. Tumor-infiltrating Tim-3+ Treg also have enhanced suppressive function and display a more effector-like phenotype. Using a novel mouse model with cell type-specific Tim-3 expression, we show here that expression of Tim-3 by Treg is sufficient to drive Treg to a more effector-like phenotype, resulting in enhanced suppressive activity and increased tumor growth. These findings may help to reconcile previous reports that some Tim-3 antibodies enhance T cell responses in vivo, while expression of Tim-3 has a cell-intrinsic ability to enhance TCR signaling and T cell activation. Thus, we propose that Tim-3 regulates anti-tumor immunity at least in part through enhancement of Treg function. To our knowledge, this is the first example in which expression of a single co-stimulatory molecule is sufficient to drive differentiation of Treg in this manner.

中文翻译：

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Tim-3的表达使幼稚Treg进入具有增强抑制活性的效应子状态

调节性T细胞（Treg）是自我耐受的关键介质，但也会限制有效的抗肿瘤免疫力。我们和其他人先前报道，浸润Treg的头颈癌（HNC）和其他肿瘤的40-60％高表达Tim-3，而在淋巴器官中大约为5％。肿瘤浸润的Tim-3 + Treg也具有增强的抑制功能，并表现出更像效应子的表型。使用具有细胞类型特异性Tim-3表达的新型小鼠模型，我们在这里显示Treg表达Tim-3足以驱动Treg达到更类似效应子的表型，从而导致抑制活性增强和肿瘤生长增加。这些发现可能有助于调和先前有关某些Tim-3抗体增强体内T细胞反应的报道，而Tim-3的表达具有增强TCR信号传导和T细胞活化的细胞内在能力。因此，我们建议Tim-3至少部分通过增强Treg功能来调节抗肿瘤免疫力。就我们所知，这是第一个例子，其中单个共刺激分子的表达足以以此方式驱动Treg分化。