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Interleukin-7 modulates anti-tumor CD8+ T cell responses via its action on host cells

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Item Type:Article
Title:Interleukin-7 modulates anti-tumor CD8+ T cell responses via its action on host cells
Creators Name:Deiser, K. and Stoycheva, D. and Bank, U. and Blankenstein, T. and Schüler, T.
Abstract:The adoptive transfer of antigen-specific CD8+ 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+ T cells. Alternatively, adjuvant effects of immunostimulatory cytokines might be exploited to improve therapeutic CD8+ T cell responses. For example, Interleukin-7 (IL-7) is a potent growth, activation and survival factor for CD8+ T cells that can be used to improve virus- and tumor-specific CD8+ T cell responses. Although direct IL-7 effects on CD8+ T cells were studied extensively in numerous models, the contribution of IL-7 receptor-competent (IL-7R+) host cells remained unclear. In the current study we provide evidence that CD8+ T cell-mediated tumor rejection in response to recombinant IL-7 (rIL-7) therapy is strictly dependent on IL-7R+ host cells. On the contrary, CD8+ 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+ T cell expansion. Unexpectedly, maximum CD8+ 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+ host cells are major targets of rIL-7 that modulate therapeutic CD8+ 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.
Keywords:Adoptive Transfer, Animal Disease Models, Biomarkers, CD8-Positive T-Lymphocytes, Cancer Vaccines, Dendritic Cells, Granulocytes, Interleukin-7, Interleukin-7 Receptors, Lymphocyte Activation, Neoplasms, Peptides, Signal Transduction, T-Lymphocyte Epitopes, T-Lymphocyte Subsets, Tumor Burden, Tumor Cell Line, Animals, Mice
Source:PLoS ONE
Publisher:Public Library of Science
Page Range:e0159690
Date:22 July 2016
Official Publication:https://doi.org/10.1371/journal.pone.0159690
PubMed:View item in PubMed

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