Regulatory T cells (Treg cells) are critical mediators of self-tolerance, but they can also limit effective anti-tumor immunity. Although under homeostasis a small fraction of Treg cells in lymphoid organs express the putative checkpoint molecule Tim-3, this protein is expressed by a much larger proportion of tumor-infiltrating Treg cells. Using a mouse model that drives cell-type-specific inducible Tim-3 expression, we show that expression of Tim-3 by Treg cells is sufficient to drive Treg cells to a more effector-like phenotype, resulting in increases in suppressive activity, effector T cell exhaustion, and tumor growth. We also show that T-reg-cell-specific inducible deletion of Tim-3 enhances anti-tumor immunity. Enhancement of Treg cell function by Tim-3 is strongly correlated with increased expression of interleukin-10 (IL-10) and a shift to a more glycolytic metabolic phenotype. Our data demonstrate that Tim-3⁺ Treg cells may be a relevant therapeutic target cell type for the treatment of cancer.

调节性 T 细胞 (Treg 细胞) 是自我耐受的关键介质，但它们也可以限制有效的抗肿瘤免疫。尽管在稳态下，淋巴器官中的一小部分 Treg 细胞表达推定的检查点分子 Tim-3，但这种蛋白质由更大比例的肿瘤浸润性 Treg 细胞表达。使用驱动细胞类型特异性诱导型 Tim-3 表达的小鼠模型，我们表明 Treg 细胞表达 Tim-3 足以驱动 Treg 细胞形成更类似于效应子的表型，从而导致抑制活性增加，效应子T细胞耗竭和肿瘤生长。我们还表明，T-reg 细胞特异性可诱导的 Tim-3 缺失增强了抗肿瘤免疫。Tim-3 对 Treg 细胞功能的增强与白细胞介素 10 (IL-10) 的表达增加和向糖酵解代谢表型的转变密切相关。我们的数据表明 Tim-3⁺ Treg 细胞可能是治疗癌症的相关治疗靶细胞类型。