CD1d-restricted iNKT constitute an important immunoregulatory T-cell subset that can be activated by α-GalCer and play a dominant role in antitumor immunity. Clinical trials with α-GalCer-pulsed moDC have shown anecdotal antitumor activity in advanced cancer. It was reported that phosphoAg (pAg)-activated Vγ9Vδ2-T can acquire professional antigen presenting cell (APC) characteristics. Considering clinical immunotherapeutic applications, Vγ9Vδ2-T APC can offer important advantages over moDC, potentially constituting an attractive novel APC platform. Here, we demonstrate that Vγ9Vδ2-T APC can act as APC for iNKT. However, this does not result from de novo synthesis of CD1d by Vγ9Vδ2-T, but critically depends on trogocytosis of CD1d-containing membrane fragments from pAg expressing cells. CD1d-expressing Vγ9Vδ2-T were able to activate iNKT in a CD1d-restricted and α-GalCer-dependent fashion. Although α-GalCer-loaded moDC outperformed Vγ9Vδ2-T APC on a per cell basis, Vγ9Vδ2-T APC possess unique features with respect to clinical immunotherapeutic application that make them an interesting platform for consideration in future clinical trials.
- Received September 27, 2013.
- Revision received March 25, 2014.
- Accepted March 27, 2014.
- Copyright © 2014, American Association for Cancer Research.