title: Interleukin-7 Modulates Anti-Tumor CD8+ T Cell Responses via Its Action on Host Cells.
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.
authors.affiliation: Institute of Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany.|Institute of Immunology, Charité-Universitaetsmedizin Berlin, Campus Benjamin Franklin, 12200 Berlin, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Deiser
authors.affiliation: Institute of Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany.|Institute of Immunology, Charité-Universitaetsmedizin Berlin, Campus Benjamin Franklin, 12200 Berlin, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Stoycheva
authors.affiliation: Institute of Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Bank
authors.affiliation: Institute of Immunology, Charité-Universitaetsmedizin Berlin, Campus Benjamin Franklin, 12200 Berlin, Germany.|Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Blankenstein
authors.affiliation: Institute of Molecular and Clinical Immunology, Medical Faculty, Otto-von-Guericke University, 39120 Magdeburg, Germany.|Institute of Immunology, Charité-Universitaetsmedizin Berlin, Campus Benjamin Franklin, 12200 Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Schüler
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D015415:Biomarkers; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D018984:Epitopes, T-Lymphocyte; D006098:Granulocytes / Q000276:immunology / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D010455:Peptides / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000378:metabolism; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D015415:Biomarkers; D019496:Cancer Vaccines; D018984:Epitopes, T-Lymphocyte; D015851:Interleukin-7; D010455:Peptides; D020395:Receptors, Interleukin-7