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Interleukin-7 Modulates Anti-Tumor CD8+ T Cell Responses via Its Action on Host Cells.
- Source :
- PLoS ONE; 7/22/2016, Vol. 11 Issue 7, p1-17, 17p
- Publication Year :
- 2016
-
Abstract
- The adoptive transfer of antigen-specific CD8<superscript>+</superscript> T cells is a promising approach for the treatment of chronic viral and malignant diseases. In order to improve adoptive T cell therapy (ATT) of cancer, recent strategies aim at the antibody-based blockade of immunosuppressive signaling pathways in CD8<superscript>+</superscript> T cells. Alternatively, adjuvant effects of immunostimulatory cytokines might be exploited to improve therapeutic CD8<superscript>+</superscript> T cell responses. For example, Interleukin-7 (IL-7) is a potent growth, activation and survival factor for CD8<superscript>+</superscript> T cells that can be used to improve virus- and tumor-specific CD8<superscript>+</superscript> T cell responses. Although direct IL-7 effects on CD8<superscript>+</superscript> T cells were studied extensively in numerous models, the contribution of IL-7 receptor-competent (IL-7R<superscript>+</superscript>) host cells remained unclear. In the current study we provide evidence that CD8<superscript>+</superscript> T cell-mediated tumor rejection in response to recombinant IL-7 (rIL-7) therapy is strictly dependent on IL-7R<superscript>+</superscript> host cells. On the contrary, CD8<superscript>+</superscript> T cell expansion is independent of host IL-7R expression. If, however, rIL-7 therapy and peptide vaccination are combined, host IL-7R signaling is crucial for CD8<superscript>+</superscript> T cell expansion. Unexpectedly, maximum CD8<superscript>+</superscript> T cell expansion relies mainly on IL-7R signaling in non-hematopoietic host cells, similar to the massive accumulation of dendritic cells and granulocytes. In summary, we provide evidence that IL-7R<superscript>+</superscript> host cells are major targets of rIL-7 that modulate therapeutic CD8<superscript>+</superscript> T cell responses and the outcome of rIL-7-assisted ATT. This knowledge may have important implications for the design and optimization of clinical ATT protocols. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 11
- Issue :
- 7
- Database :
- Complementary Index
- Journal :
- PLoS ONE
- Publication Type :
- Academic Journal
- Accession number :
- 116967607
- Full Text :
- https://doi.org/10.1371/journal.pone.0159690