Abstract 3657: Cross-regulation between the two subsets of NKT cells is dependent on interferon-gamma

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Overcoming the suppression of tumor immunity has been a major challenge in the fight against cancer. Suppression of tumor immunity is being regulated by different kinds of suppressor cells and depleting or blocking their function has been the target of immunotherapy development. One subset of immune suppressors is type II NKT cells. We have previously shown that, upon simultaneous stimulation, type I NKT cells that can promote tumor immunity and type II NKT cells cross regulate each other in vitro as well as in vivo. In some tumor models it was found that activation of type II NKT cells by sulfatide can completely abrogate the protective affect of type I NKT cell activation by alpha-galactosylceramide, leading to tumor progression and reduced survival. However the mechanism for this suppression has not been understood. By co-stimulating NKT cells in vitro, we found that type II NKT cells can inhibit the proliferation of type I NKT cells. By blocking a variety of immunregulators, we found that this suppression is dependent on interferon-gamma (IFNg). Blocking IFNg or its receptor reversed the suppression of type I NKT cell proliferation in vitro. In addition suppression was not observed in IFNgKO C57BL/6 NKT cells. It was also found that exogenous IFNg reduces the proliferation of type I NKT cells after stimulation, suggesting that IFNg is necessary for the suppression of type I NKT cells by type II NKT cells. This was unexpected as IFNg is also an effector cytokine secreted by type I NKT cells. The mechanism is under investigation. Blocking the ability of type II NKT cells to suppress type I NKT cells could shift the balance toward immune protection leading to a better tumor outcome. Citation Format: Liat Izhak, Shingo Kato, Stanley T. Parish, Masaki Terabe, Jay A. Berzofsky. Cross-regulation between the two subsets of NKT cells is dependent on interferon-gamma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3657. doi:10.1158/1538-7445.AM2014-3657