Kryczek Ilona, Wei Shuang, Zou Linhua, Altuwaijri Saleh, Szeliga Wojciech, Kolls Jay, Chang Alfred, Zou Weiping
Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA.
J Immunol. 2007 Jun 1;178(11):6730-3. doi: 10.4049/jimmunol.178.11.6730.
Th17 cells play an active role in inflammation and autoimmune diseases. However, the nature and regulation of Th17 in the context of tumor immunity remain unknown. In this study, we show that parallel to regulatory T (Treg) cells, IL-17(+) CD4(+) and CD8(+) T cells are kinetically induced in multiple tumor microenvironments in mice and humans. Treg cells play a crucial role in tumor immune pathogenesis and temper immune therapeutic efficacy. IL-2 is crucial for the production and function of Treg cells. We now show that IL-2 reduces IL-17(+) T cell differentiation in the tumor microenvironment accompanied with an enhanced Treg cell compartment in vitro and in vivo. Altogether, our work demonstrates a dynamic differentiation of IL-17(+) T cells in the tumor microenvironment, reveals a novel role for IL-2 in controlling the balance between IL-17(+) and Treg cells, and provides new insight of IL-17(+) T cells in tumor immune pathology and therapy.
辅助性T细胞17(Th17细胞)在炎症和自身免疫性疾病中发挥着积极作用。然而,在肿瘤免疫背景下Th17细胞的本质和调控机制仍不清楚。在本研究中,我们发现与调节性T(Treg)细胞类似,白细胞介素-17(IL-17)阳性的CD4和CD8 T细胞在小鼠和人类的多种肿瘤微环境中被动力学诱导。Treg细胞在肿瘤免疫发病机制中起关键作用,并影响免疫治疗效果。白细胞介素-2(IL-2)对Treg细胞的产生和功能至关重要。我们现在表明,IL-2在体外和体内均可减少肿瘤微环境中IL-17阳性T细胞的分化,同时增强Treg细胞群。总之,我们的工作证明了肿瘤微环境中IL-17阳性T细胞的动态分化,揭示了IL-2在控制IL-17阳性细胞和Treg细胞平衡方面的新作用,并为IL-17阳性T细胞在肿瘤免疫病理学和治疗中的作用提供了新的见解。