PMID- 12631593
OWN - NLM
STAT- MEDLINE
DCOM- 20031003
LR  - 20171116
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 9
IP  - 3
DP  - 2003 Mar
TI  - Tumor cyclooxygenase 2-dependent suppression of dendritic cell function.
PG  - 961-8
AB  - Dendritic cells (DCs) serve as professional antigen-presenting cells and are 
      pivotal in the host immune response to tumor antigens. To define the pathways 
      limiting DC function in the tumor microenvironment, we assessed the impact of 
      tumor cyclooxygenase (COX)-2 expression on DC activities. Bone marrow-derived DCs 
      were cultured in either tumor supernatant (TSN) or TSN from COX-2-inhibited 
      tumors. After culture, DCs were pulsed with tumor-specific peptides, and their 
      ability to generate antitumor immune responses was assessed following injection 
      into established murine lung cancer. In vitro, DC phenotype, alloreactivity, 
      antigen processing and presentation, and interleukin (IL)-10 and IL-12 secretion 
      were evaluated. DCs cultured in TSN failed to generate antitumor immune responses 
      and caused immunosuppressive effects that correlated with enhanced tumor growth. 
      However, genetic or pharmacological inhibition of tumor COX-2 expression restored 
      DC function and effective antitumor immune responses. Functional analyses 
      indicated that TSN causes a decrement in DC capacity to (a) process and present 
      antigens, (b) induce alloreactivity, and (c) secrete IL-12. Whereas TSN DCs 
      showed a significant reduction in cell surface expression of CD11c, DEC-205, MHC 
      class I antigen, MHC class II antigen, CD80, and CD86 as well as a reduction in 
      the transporter-associated proteins, transporter associated with antigen 
      processing 1 and 2, the changes in phenotype and function were not evident when 
      DCs were cultured in supernatant from COX-2-inhibited tumors. We conclude that 
      inhibition of tumor COX-2 expression or activity can prevent tumor-induced 
      suppression of DC activities.
FAU - Sharma, Sherven
AU  - Sharma S
AD  - University of California Los Angeles School of Medicine-Wadsworth Pulmonary 
      Immunology Laboratory, VA Greater Los Angeles Healthcare System, Los Angeles, CA 
      90073, USA.
FAU - Stolina, Marina
AU  - Stolina M
FAU - Yang, Seok-Chul
AU  - Yang SC
FAU - Baratelli, Felicita
AU  - Baratelli F
FAU - Lin, Jeff F
AU  - Lin JF
FAU - Atianzar, Kimberly
AU  - Atianzar K
FAU - Luo, Jie
AU  - Luo J
FAU - Zhu, Li
AU  - Zhu L
FAU - Lin, Ying
AU  - Lin Y
FAU - Huang, Min
AU  - Huang M
FAU - Dohadwala, Mariam
AU  - Dohadwala M
FAU - Batra, Raj K
AU  - Batra RK
FAU - Dubinett, Steven M
AU  - Dubinett SM
LA  - eng
GR  - CA 71818/CA/NCI NIH HHS/United States
GR  - P50 CA 90388/CA/NCI NIH HHS/United States
GR  - R01 CA 78654/CA/NCI NIH HHS/United States
GR  - R01 CA078654-02/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antigens, CD)
RN  - 0 (B7-1 Antigen)
RN  - 0 (B7-2 Antigen)
RN  - 0 (Cd86 protein, mouse)
RN  - 0 (Isoenzymes)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Oligonucleotides, Antisense)
RN  - 0 (Peptides)
RN  - 130068-27-8 (Interleukin-10)
RN  - 187348-17-0 (Interleukin-12)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
RN  - EC 1.14.99.1 (Prostaglandin-Endoperoxide Synthases)
SB  - IM
MH  - Animals
MH  - Antigens, CD/biosynthesis
MH  - B7-1 Antigen/biosynthesis
MH  - B7-2 Antigen
MH  - Blotting, Western
MH  - Cyclooxygenase 2
MH  - Cytoplasm/metabolism
MH  - Dendritic Cells/*enzymology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Immunohistochemistry
MH  - Interleukin-10/biosynthesis
MH  - Interleukin-12/biosynthesis/metabolism
MH  - Isoenzymes/*metabolism
MH  - Lung Neoplasms/enzymology
MH  - Lymphocytes/metabolism
MH  - Membrane Glycoproteins/biosynthesis
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Oligonucleotides, Antisense/pharmacology
MH  - Peptides/chemistry
MH  - Phenotype
MH  - Prostaglandin-Endoperoxide Synthases/*metabolism
MH  - Time Factors
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 2003/03/13 04:00
MHDA- 2003/10/04 05:00
CRDT- 2003/03/13 04:00
PHST- 2003/03/13 04:00 [pubmed]
PHST- 2003/10/04 05:00 [medline]
PHST- 2003/03/13 04:00 [entrez]
PST - ppublish
SO  - Clin Cancer Res. 2003 Mar;9(3):961-8.