NKT cells in Multiple Myeloma: a useful therapeutic tool?

Natural killer T (NKT) cells are T cells with features of both NK and T cells. They recognize glycolipid antigens such as agalactosylceramide (aGalCer) presented by CD1d. NKT cells can produce either a Th1 (IFNg) or a Th2 (IL4) cytokine response. Studies of the in vivo role of NKT cells in MM are limited due to a lack of a suitable mouse model. Here we investigated the functionality of NKT cells in the immune competent 5T33MM model. NKT cell numbers were similar in different organs of healthy and diseased mice. Their activity was tested in vitro by culturing liver and splenic NKT cells with DCs, pulsed with aGalCer. After 72h of co-culture, an increase in IFNg production could be measured in the supernatant of NKT cells derived from healthy and non-terminally diseased mice but not from terminally diseased mice. To confirm that the NKTs were the producers of IFNg, an intracellular cytokine staining was performed showing an increase in IFNg production in the NKTs. To analyze serum cytokine production in vivo, aGalCer alone or aGalCer pulsed DCs were injected into healthy and diseased mice 16h prior isolation.
Secretion of IFNg could be detected in healthy mice; but only a limited level was measured in diseased mice. Finally, an in vitro cytotoxicity assay using calcein-AM was performed where we found that aGal-Cer stimulated NKTs could induce lysis of 5T33MM cells. We can conclude that NKT cells can be activated in a myeloma setting and that they represent a promising cell type for immune based therapies.