|
Title
|
|
|
|
Interleukin-15-cultered dendritic cells enhance anti-tumor gamme delta T cell functions through IL-15 secretion
| |
|
Author
|
|
|
|
| |
|
Abstract
|
|
|
|
| Dendritic cell (DC) vaccination can be an effective post-remission therapy for acute myeloid leukemia (AML). Yet, current DC vaccines do not encompass the ideal stimulatory triggers for innate gamma delta (gamma delta) T cell anti-tumor activity. Promoting type 1 cytotoxic gamma delta T cells in patients with AML is, however, most interesting, considering these unconventional T cells are primed for rapid function and exert meaningful control over AML. In this work, we demonstrate that interleukin (IL)-15 DCs have the capacity to enhance the anti-tumoral functions of gamma delta T cells. IL-15 DCs of healthy donors and of AML patients in remission induce the upregulation of cytotoxicity-associated and co-stimulatory molecules on the gamma delta T cell surface, but not of co-inhibitory molecules, incite gamma delta T cell proliferation and stimulate their interferon-gamma production in the presence of blood cancer cells and phosphoantigens. Moreover, the innate cytotoxic capacity of gamma delta T cells is significantly enhanced upon interaction with IL-15 DCs, both towards leukemic cell lines and allogeneic primary AML blasts. Finally, we address soluble IL-15 secreted by IL-15 DCs as the main mechanism behind the IL-15 DC-mediated gamma delta T cell activation. These results indicate that the application of IL-15-secreting DC subsets could render DC-based anti-cancer vaccines more effective through, among others, the involvement of gamma delta T cells in the anti-leukemic immune response. |
| |
|
Language
|
|
|
|
English
| |
|
Source (journal)
|
|
|
|
Frontiers in immunology. - Place of publication unknown
| |
|
Publication
|
|
|
|
Place of publication unknown
:
2018
| |
|
ISSN
|
|
|
|
1664-3224
| |
|
DOI
|
|
|
|
10.3389/FIMMU.2018.00658
| |
|
Volume/pages
|
|
|
|
9
(2018)
, 12 p.
| |
|
Article Reference
|
|
|
|
658
| |
|
ISI
|
|
|
|
000429581700001
| |
|
Pubmed ID
|
|
|
|
29692776
| |
|
Medium
|
|
|
|
E-only publicatie
| |
|
Full text (Publisher's DOI)
|
|
|
|
| |
|
Full text (open access)
|
|
|
|
| |
|