| First Author | Janakiram NB | Year | 2017 |
| Journal | Immunology | Volume | 152 |
| Issue | 1 | Pages | 36-51 |
| PubMed ID | 28419443 | Mgi Jnum | J:250518 |
| Mgi Id | MGI:5916613 | Doi | 10.1111/imm.12746 |
| Citation | Janakiram NB, et al. (2017) Loss of natural killer T cells promotes pancreatic cancer in LSL-KrasG12D/+ mice. Immunology 152(1):36-51 |
| abstractText | 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 KrasG12D 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. |
