Thymic stromal lymphopoietin blocks early stages of breast carcinogenesis

被引:58
|
作者
Demehri, Shadmehr [1 ,2 ,3 ,4 ,5 ]
Cunningham, Trevor J. [1 ,2 ,3 ,4 ,5 ]
Manivasagam, Sindhu [5 ]
Ngo, Kenneth H. [1 ,2 ,3 ]
Tuchayi, Sara Moradi [1 ,2 ,3 ]
Reddy, Rasika [4 ,5 ]
Meyers, Melissa A. [6 ]
DeNardo, David G. [6 ]
Yokoyama, Wayne M. [5 ,7 ]
机构
[1] Harvard Univ, Sch Med, Dept Dermatol, Ctr Canc Immunol,Massachusetts Gen Hosp, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Dept Dermatol, Cutaneous Biol Res Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA
[3] Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Canc Ctr, Boston, MA USA
[4] Washington Univ, Sch Med, Div Dermatol, St Louis, MO 63110 USA
[5] Washington Univ, Sch Med, Div Rheumatol, St Louis, MO USA
[6] Washington Univ, Sch Med, Dept Med, Div Oncol, St Louis, MO 63110 USA
[7] Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA
来源
JOURNAL OF CLINICAL INVESTIGATION | 2016年 / 126卷 / 04期
关键词
CARCINOMA IN-SITU; PANCREATIC-CANCER; CELLS; KERATINOCYTES; ALLERGY; RISK; KEY;
D O I
10.1172/JCI83724
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Advances in the field of cancer immunology, including studies on tumor-infiltrating CD8(+) cytotoxic T lymphocytes (CTLs), have led to new immunotherapeutics with proven efficacy against late-stage cancers. However, the antitumor potential of the immune system in targeting early-stage cancers remains uncertain. Here, we demonstrated that both genetic and chemical induction of thymic stromal lymphopoietin (TSLP) at a distant site leads to robust antitumor immunity against spontaneous breast carcinogenesis in mice. Breast tumors exposed to high circulating levels of TSLP were arrested at an early adenoma-like stage and were prevented from advancing to late carcinoma and metastasis. Additionally, CD4(+) Th2 cells mediated the antitumor effects of TSLP, challenging the notion that Th2 cells only promote cancer. We also discovered that TSLP is expressed by the breast tumor cells themselves and acts to block breast cancer promotion. Moreover, TSLP-induced immunity also blocked early stages of pancreatic cancer development. Together, our findings demonstrate that TSLP potently induces immunity directed against early stages of breast cancer development without causing inflammation in the normal breast tissue. Moreover, our results highlight a previously unappreciated function of the immune system in controlling the early development of cancer and establish a fundamental role for TSLP and Th2 cells in tumor immunity against early-stage cancers.
引用
收藏
页码:1458 / 1470
页数:13
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