PMID- 24598451
OWN - NLM
STAT- MEDLINE
DCOM- 20141106
LR  - 20211021
IS  - 1537-4513 (Electronic)
IS  - 1524-9557 (Print)
IS  - 1524-9557 (Linking)
VI  - 37
IP  - 3
DP  - 2014 Apr
TI  - Ovarian tumor ascites CD14+ cells suppress dendritic cell-activated CD4+ T-cell 
      responses through IL-10 secretion and indoleamine 2,3-dioxygenase.
PG  - 163-9
LID - 10.1097/CJI.0000000000000030 [doi]
AB  - The observation that Th17 infiltration in ovarian cancer correlates with markedly 
      improved survival has prompted the question of whether ovarian tumor 
      antigen-specific Th17 responses could be stimulated by tumor vaccination. 
      Dendritic cells (DCs) treated with IL-15 and an inhibitor of p38 MAPK signaling 
      (DC(IL-15/p38inhib)) bias T-cell responses toward a Th1/Th17 phenotype, raising 
      the prospect of therapeutic vaccination; however, significant barriers remain. 
      Tumor vaccines, including DC vaccination, usually stimulate immune responses, but 
      the lack of clinical responses in cancer patients has been disappointing. 
      Possible reasons may include an inability of antitumor T cells to migrate into 
      the tumor microenvironment, and an inability of T cells to retain effector 
      function in the face of tumor-associated immune suppression. We found that 
      ovarian tumor antigen-specific CD4(+) T cells induced by DC(IL-15/p38inhib) 
      migrated in response to CXCL12 and CCL22 (both highly expressed in ovarian 
      cancer) and to ascites CD14(+) myeloid cells. Cocultures showed that ascites 
      CD14(+) cells markedly suppressed antigen-specific CD4(+) T responses, but 
      suppression could be alleviated by treatment with anti-IL-10 or inhibition of 
      indoleamine 2,3-dioxygenase. These results suggest that the efficacy of DC 
      vaccination against ovarian cancer may be boosted by agents that inhibit 
      tumor-associated CD14(+) myeloid cell suppression or indoleamine 2,3-dioxygenase 
      activity.
FAU - Goyne, Hannah E
AU  - Goyne HE
AD  - Departments of *Microbiology and Immunology daggerObstetrics and Gynecology, 
      University of Arkansas for Medical Sciences, Little Rock, AR.
FAU - Stone, Pamela J B
AU  - Stone PJ
FAU - Burnett, Alexander F
AU  - Burnett AF
FAU - Cannon, Martin J
AU  - Cannon MJ
LA  - eng
GR  - UL1 RR029884/RR/NCRR NIH HHS/United States
GR  - NIHUL1RR029884/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Immunother
JT  - Journal of immunotherapy (Hagerstown, Md. : 1997)
JID - 9706083
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Cancer Vaccines)
RN  - 0 (Cytokines)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 0 (Lipopolysaccharide Receptors)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Antigens, Neoplasm/immunology
MH  - Ascites/*immunology
MH  - CD4-Positive T-Lymphocytes/*immunology
MH  - Cancer Vaccines
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Cytokines/*immunology
MH  - Dendritic Cells/immunology
MH  - Female
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/*immunology
MH  - Lipopolysaccharide Receptors/*immunology
MH  - Ovarian Neoplasms/*immunology
MH  - p38 Mitogen-Activated Protein Kinases/antagonists & inhibitors/immunology
PMC - PMC3954539
MID - NIHMS557957
COIS- Conflicts of Interest: The remaining authors declare no financial conflicts of 
      interest with regard to this work.
EDAT- 2014/03/07 06:00
MHDA- 2014/11/07 06:00
PMCR- 2015/04/01
CRDT- 2014/03/07 06:00
PHST- 2014/03/07 06:00 [entrez]
PHST- 2014/03/07 06:00 [pubmed]
PHST- 2014/11/07 06:00 [medline]
PHST- 2015/04/01 00:00 [pmc-release]
AID - 10.1097/CJI.0000000000000030 [doi]
PST - ppublish
SO  - J Immunother. 2014 Apr;37(3):163-9. doi: 10.1097/CJI.0000000000000030.