Oxidized-Desialylated Low-Density Lipoprotein Inhibits the Antitumor Functions of Lymphokine Activated Killer Cells

JesÃs S.Aguilar Diáz De Leãn, Honor L. Glenn, Mark Knappenberger, Chad R. Borges

Research output: Contribution to journalArticlepeer-review

Abstract

Elevated concentrations of circulating low density lipoprotein (LDL) that is abnormally oxidized and desialylated is both a precursor to and a hallmark of atherosclerosis. Peripheral blood mononuclear cells (PBMCs) treated in vitro with interleukin-2 (IL-2) become lymphokine activated killer (LAK) cells, the primary effectors of which are NK cells and NKT cells. LAK cells display antitumor functions such as increased cytotoxicity and IFN-γ production, and they have been evaluated as a potential cancer therapeutic. Atherosclerotic processes may influence innate immunity against cancer. Because prior studies have shown that low density lipoprotein (LDL) reduces T-cell and NK cell antitumor functions, we asked whether oxidized-desialylated LDL affects the functionality of LAK cells in vitro. We show here that LAK cells take up oxidized-desialylated LDL to a significantly greater extent than native LDL over a period of 72 hours. This resulted in a significant downregulation of LAK cell cytotoxicity against K562 cells. In particular, the expression of IFN-γ, CD56, and NKG2D were reduced upon oxidized-desialylated LDL treatment of LAK cells and, conversely, their expression was enhanced with native LDL. It was also observed that as the number of CD56 and NKG2D positive cells decreased upon treatment with oxidized-desialylated LDL, the number of CD3 positive cells increased in proportion. Additionally, only a slight inhibition of LAK cell cytotoxicity was observed with desialylation alone of LDL, and no significant inhibition was observed with oxidation alone of LDL. Thus, this study describes a new role of oxidized-desialylated LDL as an inhibitor of the antitumor functions of LAK cells. These observations have implications for how atherosclerosis processes, namely oxidation and desialylation of LDL, may influence LAK cell antitumor activity.

Original languageEnglish (US)
Pages (from-to)4993-5004
Number of pages12
JournalJournal of Cancer
Volume12
Issue number16
DOIs
StatePublished - 2021

Keywords

  • Atherosclerosis
  • Cancer
  • Lymphokine activated killer (lak) cells
  • Oxidized-desialylated low-density lipoprotein (ldl)

ASJC Scopus subject areas

  • Oncology

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