Original ArticleNivolumab augments antitumor activity of invariant natural killer T cells

ABSTRACT【Objective】Programmed death-1 (PD-1) negatively regulates T cell functions. Nivolumab is a clinically approved anti-PD-1 antibody that inhibits PD-1 signaling, thus enhancing T cell activity. Although nivolumab has been widely used in the treatment of various cancers, it is only effective in limited patients. To develop better treatment options, combination therapies with nivolumab have been in the spotlight. Natural killer T (NKT) cell-based immunotherapy involves activation of NKT cells by injection of ligand-loaded dendritic cells, thereby inducing antitumor immunity. In this study, we examined whether nivolumab treatment enhances NKT cell activity in tumor immunity to investigate the potential use of nivolumab in NKT cell-based immunotherapy as a combination therapy to improve the current treatment options. 【Methods】Peripheral blood mononuclear cells were obtained from healthy donors. NKT cells were cultured with α-galactosylceramide for 6 days. The functions of purified NKT cells in the presence or absence of nivolumab were evaluated by flow cytometry and a cytometric bead array. NK cell-mediated cytotoxic activities were evaluated using a transwell system to investigate the adjuvant effects of activated NKT cells. 【Results and conclusion】PD-1 expression in NKT cells was upregulated in response to T cell receptor stimulation. Although nivolumab treatment had no impact on NKT cell proliferation, nivolumab-treated NKT cells exhibited increased production of cytokines and Granzyme B. Furthermore, nivolumab treatment significantly enhanced the cytotoxic activity of NKT cells against K562 or A549 cells and had an adjuvant effect on natural killer cell function. Taken together, these data indicate that combination of NKT cell-based immunotherapy and nivolumab treatment could be a better treatment option for various cancer.