PMID- 27447484
OWN - NLM
STAT- MEDLINE
DCOM- 20170724
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 11
IP  - 7
DP  - 2016
TI  - Interleukin-7 Modulates Anti-Tumor CD8+ T Cell Responses via Its Action on Host 
      Cells.
PG  - e0159690
LID - 10.1371/journal.pone.0159690 [doi]
LID - e0159690
AB  - 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.
FAU - Deiser, Katrin
AU  - Deiser K
AD  - Institute of Molecular and Clinical Immunology, Medical Faculty, 
      Otto-von-Guericke University, 39120 Magdeburg, Germany.
AD  - Institute of Immunology, Charite-Universitaetsmedizin Berlin, Campus Benjamin 
      Franklin, 12200 Berlin, Germany.
FAU - Stoycheva, Diana
AU  - Stoycheva D
AD  - Institute of Molecular and Clinical Immunology, Medical Faculty, 
      Otto-von-Guericke University, 39120 Magdeburg, Germany.
AD  - Institute of Immunology, Charite-Universitaetsmedizin Berlin, Campus Benjamin 
      Franklin, 12200 Berlin, Germany.
FAU - Bank, Ute
AU  - Bank U
AD  - Institute of Molecular and Clinical Immunology, Medical Faculty, 
      Otto-von-Guericke University, 39120 Magdeburg, Germany.
FAU - Blankenstein, Thomas
AU  - Blankenstein T
AD  - Institute of Immunology, Charite-Universitaetsmedizin Berlin, Campus Benjamin 
      Franklin, 12200 Berlin, Germany.
AD  - Max-Delbruck-Center for Molecular Medicine, 13125 Berlin, Germany.
FAU - Schuler, Thomas
AU  - Schuler T
AD  - Institute of Molecular and Clinical Immunology, Medical Faculty, 
      Otto-von-Guericke University, 39120 Magdeburg, Germany.
AD  - Institute of Immunology, Charite-Universitaetsmedizin Berlin, Campus Benjamin 
      Franklin, 12200 Berlin, Germany.
LA  - eng
PT  - Journal Article
DEP - 20160722
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Epitopes, T-Lymphocyte)
RN  - 0 (Interleukin-7)
RN  - 0 (Peptides)
RN  - 0 (Receptors, Interleukin-7)
SB  - IM
MH  - Adoptive Transfer
MH  - Animals
MH  - Biomarkers
MH  - CD8-Positive T-Lymphocytes/drug effects/*immunology/*metabolism
MH  - Cancer Vaccines
MH  - Cell Line, Tumor
MH  - Dendritic Cells/immunology/metabolism
MH  - Disease Models, Animal
MH  - Epitopes, T-Lymphocyte
MH  - Granulocytes/immunology/metabolism
MH  - Interleukin-7/*metabolism/pharmacology
MH  - Lymphocyte Activation/drug effects
MH  - Mice
MH  - Mice, Knockout
MH  - Mice, Transgenic
MH  - Neoplasms/*immunology/*metabolism/pathology/therapy
MH  - Peptides/immunology
MH  - Receptors, Interleukin-7/metabolism
MH  - Signal Transduction
MH  - T-Lymphocyte Subsets/immunology/metabolism
MH  - Tumor Burden
PMC - PMC4957759
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2016/07/23 06:00
MHDA- 2017/07/25 06:00
PMCR- 2016/07/22
CRDT- 2016/07/23 06:00
PHST- 2016/03/21 00:00 [received]
PHST- 2016/07/05 00:00 [accepted]
PHST- 2016/07/23 06:00 [entrez]
PHST- 2016/07/23 06:00 [pubmed]
PHST- 2017/07/25 06:00 [medline]
PHST- 2016/07/22 00:00 [pmc-release]
AID - PONE-D-16-11709 [pii]
AID - 10.1371/journal.pone.0159690 [doi]
PST - epublish
SO  - PLoS One. 2016 Jul 22;11(7):e0159690. doi: 10.1371/journal.pone.0159690. 
      eCollection 2016.