Human Cytokine-Induced Killer Cells Specifically Infiltrated and Retarded the Growth of the Inoculated Human Cholangiocarcinoma Cells in SCID Mice

Abstract

Cytokine-induced killer (CIK) cells were examined for safety and efficacy for cholangiocarcinoma treatment. Several conditions of human CIK cells were examined using ex vivo cytotoxic assay and SCID mice pre-inoculated with cholangiocarcinoma cells. We monitored the ex vivo cytotoxicity, tumor sizes and immunohistochemistry. Optimal tumor suppression was observed when CIK cells were pre-exposed to dendritic cells (DCs). Unexpectedly, pulsing of tumor RNA to DCs rendered the co-culturing CIK cells ineffective and raised the proportion of CD4⁺CD25⁺ subset. The use of CD3⁺CD56⁺ subset instead of the whole population of CIK cells for the co-culture with RNA-pulsed DCs restored the efficacy. Tumor-infiltrating human CD3⁺ cells were observed from day 2 – 14. The CD3⁺CD56⁺ cells are logical candidates for clinical trial while the DC-co-cultured CIK cells produced similar efficacy and more feasible for clinical application. The RNA pulsation of DCs up-regulated the regulatory subset of CIK cells and abrogated the anti-tumor efficacy.

Keywords:

• Cytokine-induced killer cells
• Cholangiocarcinoma
• Animal experiment

ABBREVIATIONS
CIK	=	cytokine-induced killer cell
DC	=	dendritic cell
CCA	=	cholangiocarcinoma
Treg	=	Regulatory T cell
PBMCs	=	Peripheral blood mononuclear cells

ABBREVIATIONS
CIK	=	cytokine-induced killer cell
DC	=	dendritic cell
CCA	=	cholangiocarcinoma
Treg	=	Regulatory T cell
PBMCs	=	Peripheral blood mononuclear cells