Enhancement of cancer-type specific cytotoxicity of natural killer cells via pre-conditioning with cancer cell culture medium

Abstract

Recently, we have established a method for culturing NK cell-enriched lymphocytes (NKELs) with high anti-cancer activity. These NKELs are found to be highly cytotoxic against various types of cancer cells, and even the extracellular vesicles derived from those NKELs were also demonstrated high anti-cancer activity. In the present study, to find a way to enhance cancer type specificity of these NKELs, the impact of tumor cell-priming of these NKELs on their cytotoxic effect against particular type of cancer cells was investigated. According to our data, when these NKELs were primed with conditioned media (CM) from three different lines of liver cancer cell lines, their cytotoxicity against liver cancer cell lines was significantly increased compared to that of the NKELs without priming. Based on cytokine arrays of the tumor CM and subsequent network analysis, 6 proteins were selected as a potential candidate factors that facilitated the liver cancer cell-specific priming of those NKELs. When these 6 candidate proteins (human recombinant proteins) were separately applied to prime NKELs, 2 out of 6 proteins (DKK1 and THBS1) showed enhanced liver cancer-specific cytotoxicity. With further optimization and elucidation of the underlying mechanisms, it may be possible to prime NKELs for learned cancer type specificity.

Keywords

• Natural killer cell-enriched lymphocytes (NKELs)
• conditioned medium (CM)
• Tumor priming
• Liver cancer
• Dickkopf WNT signaling pathway inhibitor 1 (DKK1)
• Thrombospondin 1 (THBS1)