PMID- 19417739
OWN - NLM
STAT- MEDLINE
DCOM- 20091013
LR  - 20211020
IS  - 1525-0024 (Electronic)
IS  - 1525-0016 (Print)
IS  - 1525-0016 (Linking)
VI  - 17
IP  - 7
DP  - 2009 Jul
TI  - Therapeutic immunity by adoptive tumor-primed CD4(+) T-cell transfer in 
      combination with in vivo GITR ligation.
PG  - 1274-81
LID - 10.1038/mt.2009.100 [doi]
AB  - Tumor-primed CD4(+) T cells from splenocytes of tumor-rejection mice in 
      combination with in vivo glucocorticoid-induced tumor necrosis factor receptor 
      (GITR) ligation (the combination therapy) elicited effective host CD8(+) T 
      cell-dependent therapeutic immunity against a murine breast tumor. GITR ligation 
      in vitro enhanced tumor-primed CD4(+) T-cell activity and partially abrogated 
      regulatory T cells (Treg) suppressor function. Dendritic cells (DCs) from 
      tumor-draining lymph nodes (TDLNs) of tumor-bearing mice treated by the 
      combination therapy stimulated Ag-specific T cells and produced interleukin 
      (IL)-12 ex vivo. Whereas tumor-primed CD4(+) T cells or in vivo GITR ligation 
      alone induced a tumor-specific interferon (IFN)-gamma-producing cellular 
      response, the combination therapy enhanced and sustained it. Furthermore, the 
      combination therapy in vivo attenuated Treg's ability to suppress IL-12 
      production by DCs and IFN-gamma production by effectors ex vivo. Importantly, 
      tumor-primed CD4(+) CD25(-) T cells from splenocytes of untreated tumor-bearing 
      mice in combination with in vivo GITR ligation also elicited an effective 
      therapeutic effect in this model. These data suggest that the combination therapy 
      may improve DC function, accentuate tumor-specific T-cell responses, and 
      attenuate Treg suppressor function, thereby eliciting effective therapeutic 
      immunity.
FAU - Liu, Zuqiang
AU  - Liu Z
AD  - Department of Dermatology, University of Pittsburgh School of Medicine, 
      Pennsylvania, USA.
FAU - Tian, Shenghe
AU  - Tian S
FAU - Falo, Louis D Jr
AU  - Falo LD Jr
FAU - Sakaguchi, Shimon
AU  - Sakaguchi S
FAU - You, Zhaoyang
AU  - You Z
LA  - eng
GR  - R01 CA108813/CA/NCI NIH HHS/United States
GR  - P50 CA121973/CA/NCI NIH HHS/United States
GR  - CA10662/CA/NCI NIH HHS/United States
GR  - CA121973/CA/NCI NIH HHS/United States
GR  - R01CA108813/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090505
PL  - United States
TA  - Mol Ther
JT  - Molecular therapy : the journal of the American Society of Gene Therapy
JID - 100890581
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Glucocorticoid-Induced TNFR-Related Protein)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/therapeutic use
MH  - Breast Neoplasms/*immunology/*therapy
MH  - CD4-Positive T-Lymphocytes/*immunology/*transplantation
MH  - CD8-Positive T-Lymphocytes/immunology
MH  - Dendritic Cells/immunology
MH  - Female
MH  - Glucocorticoid-Induced TNFR-Related Protein/*metabolism
MH  - Immunity, Cellular/drug effects/immunology
MH  - Immunotherapy, Adoptive/*methods
MH  - Interferon-gamma/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Receptors, Tumor Necrosis Factor/immunology
MH  - T-Lymphocytes, Regulatory/immunology
PMC - PMC2731416
MID - NIHMS120820
EDAT- 2009/05/07 09:00
MHDA- 2009/10/14 06:00
PMCR- 2010/07/01
CRDT- 2009/05/07 09:00
PHST- 2009/05/07 09:00 [entrez]
PHST- 2009/05/07 09:00 [pubmed]
PHST- 2009/10/14 06:00 [medline]
PHST- 2010/07/01 00:00 [pmc-release]
AID - S1525-0016(16)31839-1 [pii]
AID - 10.1038/mt.2009.100 [doi]
PST - ppublish
SO  - Mol Ther. 2009 Jul;17(7):1274-81. doi: 10.1038/mt.2009.100. Epub 2009 May 5.