| First Author | Choi DH | Year | 2011 |
| Journal | Cancer Res | Volume | 71 |
| Issue | 24 | Pages | 7442-51 |
| PubMed ID | 22028323 | Mgi Jnum | J:178846 |
| Mgi Id | MGI:5300412 | Doi | 10.1158/0008-5472.CAN-11-1459 |
| Citation | Choi DH, et al. (2011) Dendritic Cell Internalization of alpha-Galactosylceramide from CD8 T Cells Induces Potent Antitumor CD8 T-cell Responses. Cancer Res 71(24):7442-51 |
| abstractText | Dendritic cells (DC) present alpha-galactosylceramide (alphaGalCer) to invariant T-cell receptor-expressing natural killer T cells (iNKT) activating these cells to secrete a variety of cytokines, which in turn results in DC maturation and activation of other cell types, including NK cells, B cells, and conventional T cells. In this study, we showed that alphaGalCer-pulsing of antigen-activated CD8 T cells before adoptive transfer to tumor-bearing mice caused a marked increase in donor T-cell proliferation, precursor frequency, and cytotoxic lymphocyte activity. This effect was interleukin (IL)-2 dependent and involved both natural killer T cells (NKT) and DCs, as mice lacking IL-2, NKTs, and DCs lacked any enhanced response to adoptively transferred alphaGalCer-loaded CD8 T cells. iNKT activation was mediated by transfer of alphaGalCer from the cell membrane of the donor CD8 T cells onto the alphaGalCer receptor CD1d which is present on host DCs. alphaGalCer transfer was increased by prior activation of the donor CD8 T cells and required AP-2-mediated endocytosis by host DCs. In addition, host iNKT cell activation led to strong IL-2 synthesis, thereby increasing expansion and differentiation of donor CD8 T cells. Transfer of these cells led to improved therapeutic efficacy against established solid tumors in mice. Thus, our findings illustrate how alphaGalCer loading of CD8 T cells after antigen activation in vitro may leverage the therapeutic potential of adoptive T-cell therapies. Cancer Res; 71(24); 7442-51. (c)2011 AACR. |
