Co-operation of α-galactosylceramide-loaded tumour cells and TLR9 agonists induce potent anti-tumour responses in a murine colon cancer model.

Abstract

Dendritic cells (DCs) and invariant natural killer T (iNKT) cells play important roles in linking innate immunity and adaptive immunity. Mature DCs activated by Toll-like receptor (TLR) agonists directly activate iNKT cells and the iNKT ligand α-galactosylceramide (α-Galcer) can induce DC maturation, resulting in enhanced protective immune responses. In the present study, we aimed to boost anti-tumour immunity in a murine colon cancer model by synergizing DCs and iNKT cells using α-Galcer-loaded tumour cells (tumour-Gal) and the TLR9 agonist cytosine-phosphorothioate-guanine (CpG1826). The vaccine strategy was sufficient to inhibit growth of established tumours and prolonged survival of tumour-bearing mice. Importantly, the immunization induced an adaptive memory immune response as the survivors from primary tumour inoculations were resistant to a tumour re-challenge. Furthermore, injection of tumour-Gal with CpG1826 resulted in iNKT cell activation and DC maturation as defined by interferon (IFN)-γ secretion by iNKT, natural killer (NK) cells and interleukin (IL)-12 by DCs. Immunohistochemistry analysis revealed that cluster of differentiation (CD)4(+) T-cells and CD8(+) T-cells played important roles in anti-tumour immunity. Additionally, the vaccine redirected Th2 (T-helper cell type 2) responses toward Th1 (T-helper cell type 1) responses with increases in IL-2, IFN-γ expression and decreases in IL-4 and IL-5 expression after immunization with tumour-Gal with CpG1826. Taken together, our results demonstrated a novel vaccination by synergizing tumour-Gal and CpG1826 against murine colon cancer, which can be further developed as tumour-specific immunotherapy against human cancer.

DOI: 10.1042/BJ20150129

Cite this paper

@article{Dong2016CooperationO, title={Co-operation of α-galactosylceramide-loaded tumour cells and TLR9 agonists induce potent anti-tumour responses in a murine colon cancer model.}, author={Tiangeng Dong and Tuo Yi and Mengxuan Yang and Shengli Lin and Wenxiang Li and Xingyuan Xu and Jianwei Hu and Lijun Jia and Xinqiang Hong and Weixin Niu}, journal={The Biochemical journal}, year={2016}, volume={473 1}, pages={7-19} }