AI Article Synopsis
- Researchers found that GIFT-21, a fusion of GM-CSF and IL-21, enhances the immune response in myeloid cells, leading to the creation of unique dendritic cells (DCs) that show increased markers associated with immune activation.
- These GIFT-21 DCs produce higher levels of key cytokines and effectively stimulate CD8(+) T cells, which are important for fighting tumors, particularly in the context of cancer.
- In tests using mice, treatment with GIFT-21 DCs slowed the growth of certain cancers, highlighting their potential use as a new cancer therapy by presenting tumor antigens and activating T cells.
Article Abstract
We have previously shown that the fusion of GM-CSF and IL-21 (GIFT-21) possesses a potent immune stimulatory effect on myeloid cells. In this study, we define the effect of GIFT-21 on naive murine monocytes (GIFT-21 dendritic cells [DCs]), which express increased levels of Gr-1, CD45R, MHC class I, CD80, CD86, and CXCR4 and suppress CD11c and MHC class II. Compared with conventional dendritic cells, GIFT-21 DCs produced substantially more CCL2, IL-6, TNF-α, and IFN-α and induced significantly greater production of IFN-γ by CD8(+) T cells in MHC class I-restricted Ag presentation assays. B16 melanoma and D2F2 Neu breast cancer growth was inhibited in mice treated with Ag-naive GIFT-21 DCs. This effect was lost in CD8(-/-) and CCR2(-/-) mice and when mice were treated with β(2)-microglobulin-deficient GIFT-21 DCs, indicating that GIFT-21 DCs migrated to and sampled from the tumors to present tumor Ags to CCL2 recruited CD8(+) T cells via MHC class I. We propose that autologous GIFT-21 DCs may serve as a cell therapy platform for the treatment of cancer.
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| http://dx.doi.org/10.4049/jimmunol.1002201 | DOI Listing |
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