Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Institute of Infection Immunology, TWINCORE, Centre for Experimental and Clinical Infection Research, Hannover, Germany.
Eur J Immunol. 2015 Jun;45(6):1654-66. doi: 10.1002/eji.201445058. Epub 2015 Apr 14.
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-γ 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.
结直肠癌（CRC）是全球最常见的肿瘤类型之一，肿瘤浸润 T 细胞对于抗肿瘤免疫至关重要。我们之前证明 CRC 患者的 Treg 细胞抑制常规 T 细胞的跨内皮迁移。然而，局部 Treg 细胞是否影响淋巴细胞向结肠肿瘤的迁移仍不清楚。通过将表达白喉毒素受体的 APC(Min/+)小鼠与 FoxP3 启动子控制下的调节性 T 细胞缺失小鼠进行杂交，我们能够选择性地在荷瘤小鼠中耗尽 Treg 细胞，并研究这些细胞对常规 T 细胞浸润肠道肿瘤的影响。Treg 细胞的短期耗竭导致肿瘤中 T 细胞的频率显著增加，这归因于 Treg 细胞耗竭肿瘤中 T 细胞的浸润和增殖增加。我们还证明 Treg 细胞耗竭肿瘤中趋化因子 CXCL9 和 CXCL10 的选择性增加，这伴随着 CXCR3(+)T 细胞的积累和 IFN-γ mRNA 表达的增加。总之，Treg 细胞的耗竭增加了肠道肿瘤中常规 T 细胞的积累，靶向 Treg 细胞可能是一种潜在的抗肿瘤免疫疗法，它不仅影响 T 细胞的效应功能，还影响它们向肿瘤的募集。
