Cutting edge: Th17 and regulatory T cell dynamics and the regulation by IL-2 in the tumor microenvironment

被引:331
作者
Kryczek, Ilona
Wei, Shuang
Zou, Linhua
Altuwaijri, Saleh
Szeliga, Wojciech
Kolls, Jay
Chang, Alfred
Zou, Weiping
机构
[1] Univ Michigan, Sch Med, Dept Surg, Ann Arbor, MI 48109 USA
[2] Univ Pittsburgh, Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA
关键词
D O I
10.4049/jimmunol.178.11.6730
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:6730 / +
页数:3
相关论文
共 29 条
[1]   Interleukin-23 promotes a distinct CD4 T cell activation state characterized by the production of interleukin-17 [J].
Aggarwal, S ;
Ghilardi, N ;
Xie, MH ;
de Sauvage, FJ ;
Gurney, AL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (03) :1910-1914
[2]   IL-2 administration increases CD4+CD25hi Foxp3+ regulatory T cells in cancer patients [J].
Ahmadzadeh, M ;
Rosenberg, ST .
BLOOD, 2006, 107 (06) :2409-2414
[3]   Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells [J].
Bettelli, E ;
Carrier, YJ ;
Gao, WD ;
Korn, T ;
Strom, TB ;
Oukka, M ;
Weiner, HL ;
Kuchroo, VK .
NATURE, 2006, 441 (7090) :235-238
[4]  
CHAN WCW, 2000, P SOC PHOTO-OPT INS, V1, P2
[5]   Interleukin-23 rather than interleukin-12 is the critical cytokine for autoimmune inflammation of the brain [J].
Cua, DJ ;
Sherlock, J ;
Chen, Y ;
Murphy, CA ;
Joyce, B ;
Seymour, B ;
Lucian, L ;
To, W ;
Kwan, S ;
Churakova, T ;
Zurawski, S ;
Wiekowski, M ;
Lira, SA ;
Gorman, D ;
Kastelein, RA ;
Sedgwick, JD .
NATURE, 2003, 421 (6924) :744-748
[6]   Specific recruitment of regulatory T cells in ovarian carcinoma fosters immune privilege and predicts reduced survival [J].
Curiel, TJ ;
Coukos, G ;
Zou, LH ;
Alvarez, X ;
Cheng, P ;
Mottram, P ;
Evdemon-Hogan, M ;
Conejo-Garcia, JR ;
Zhang, L ;
Burow, M ;
Zhu, Y ;
Wei, S ;
Kryczek, I ;
Daniel, B ;
Gordon, A ;
Myers, L ;
Lackner, A ;
Disis, ML ;
Knutson, KL ;
Chen, LP ;
Zou, WP .
NATURE MEDICINE, 2004, 10 (09) :942-949
[7]   Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity [J].
Curiel, TJ ;
Wei, S ;
Dong, HD ;
Alvarez, X ;
Cheng, P ;
Mottram, P ;
Krzysiek, R ;
Knutson, KL ;
Daniel, B ;
Zimmermann, MC ;
David, O ;
Burow, M ;
Gordon, A ;
Dhurandhar, N ;
Myers, L ;
Berggren, R ;
Hemminki, A ;
Alvarez, RD ;
Emilie, D ;
Curiel, DT ;
Chen, LP ;
Zou, WP .
NATURE MEDICINE, 2003, 9 (05) :562-567
[8]   Opinion - Diversification of T-helper-cell lineages: finding the family root of IL-17-producing cells [J].
Dong, C .
NATURE REVIEWS IMMUNOLOGY, 2006, 6 (04) :329-333
[9]   Interleukin 2 signaling is required for CD4+ regulatory T cell function [J].
Furtado, GC ;
de Lafaille, MAC ;
Kutchukhidze, N ;
Lafaille, JJ .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (06) :851-857
[10]   Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages [J].
Harrington, LE ;
Hatton, RD ;
Mangan, PR ;
Turner, H ;
Murphy, TL ;
Murphy, KM ;
Weaver, CT .
NATURE IMMUNOLOGY, 2005, 6 (11) :1123-1132