Loss of natural killer T cells promotes pancreatic cancer in LSL-KrasG12D/+ mice

被引：53

作者：

Janakiram, Naveena B. ^{[1
]}

Mohammed, Altaf ^{[1
,4
]}

Bryant, Taylor ^{[1
]}

Ritchie, Rebekah ^{[1
]}

Stratton, Nicole ^{[1
]}

Jackson, Lydgia ^{[2
]}

Lightfoot, Stan ^{[1
]}

Benbrook, Doris M. ^{[3
]}

Asch, Adam S. ^{[1
]}

Lang, Mark L. ^{[2
]}

Rao, Chinthalapally V. ^{[1
]}

机构：

[1] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Ctr Canc Prevent & Drug Dev,Hematol Oncol Sect,St, Oklahoma City, OK USA

[2] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73190 USA

[3] Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA

[4] NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, Rockville, MD USA

来源：

IMMUNOLOGY | 2017年 / 152卷 / 01期

基金：

美国国家卫生研究院;

关键词：

microsomal prostaglandin E synthase-1; natural killer T cells; pancreatic cancer; prevention; treatment; TUMOR PROGRESSION; COLON; NK; MACROPHAGES; SUPPRESSION; EXPRESSION;

D O I：

10.1111/imm.12746

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

The role of the unique T-cell population, natural killer T (NKT) cells, which have similar functions to NK cells in pancreatic cancer (PC), is not yet evaluated. To address the regulatory roles of NKT cells on tumour progression through tumour-associated macrophages (TAM) and their production of microsomal prostaglandin E synthase-1 (mPGES-1) and 5-lipoxygenase (5-LOX) in (Kras)-driven pancreatic tumour (KPT) progression, we crossed CD1d(-/-) mice deficient in both invariant and variant NKT cells with the Kras(G12D) mice. Loss of NKT cells significantly increased pancreatic intraepithelial neoplasia (PanIN) lesions and also increased 5-LOX and mPGES-1 expression in M2-type macrophages and cancer stem-like cells in pancreatic tumours. Pharmacological inhibition of mPGES-1 and 5-LOX in M2 macrophages with specific inhibitor YS-121 in KPT-CD1d(-/-) mice decreased PanIN lesions and suppressed tumour growth in association with elevated levels of active CD8a cells. Hence, NKT cells regulate PC by modulating TAMs (M2) through mPGES-1 and 5-LOX; and the absence of NKT cells leads to aggressive development of PC.

引用

页码：36 / 51

页数：16

共 28 条

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