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Inhibition of cyclooxygenase-2 enhances immunotherapy against experimental brain tumors.

Eberstål, Sofia LU ; Badn, Wiaam LU ; Fritzell, Sara LU ; Esbjörnsson, Magnus; Darabi, Anna LU ; Visse, Edward LU and Siesjö, Peter LU (2012) In Cancer immunology, immunotherapy : CII 61(8). p.1191-1199
Abstract
Glioblastoma multiforme is the most common and aggressive malignant brain tumor in humans, and the prognosis is very poor despite conventional therapy. Immunotherapy represents a novel treatment approach, but the effect is often weakened by release of immune-suppressive molecules such as prostaglandins. In the current study, we investigated the effect of immunotherapy with irradiated interferon-γ (IFN-γ)-secreting tumor cells and administration of the selective cyclooxygease-2 (COX-2) inhibitor parecoxib as treatment of established rat brain tumors. COX-2 inhibition and immunotherapy significantly enhanced the long-term cure rate (81% survival) compared with immunotherapy alone (19% survival), and there was a significant increase in plasma... (More)
Glioblastoma multiforme is the most common and aggressive malignant brain tumor in humans, and the prognosis is very poor despite conventional therapy. Immunotherapy represents a novel treatment approach, but the effect is often weakened by release of immune-suppressive molecules such as prostaglandins. In the current study, we investigated the effect of immunotherapy with irradiated interferon-γ (IFN-γ)-secreting tumor cells and administration of the selective cyclooxygease-2 (COX-2) inhibitor parecoxib as treatment of established rat brain tumors. COX-2 inhibition and immunotherapy significantly enhanced the long-term cure rate (81% survival) compared with immunotherapy alone (19% survival), and there was a significant increase in plasma IFN-γ levels in animals treated with the combined therapy, suggesting a systemic T helper 1 immune response. COX-2 inhibition alone, however, did neither induce cure nor prolonged survival. The tumor cells were identified as the major source of COX-2 both in vivo and in vitro, and unmodified tumor cells produced prostaglandin E(2) in vitro, while the IFN-γ expressing tumor cells secreted significantly lower levels. In conclusion, we show that immunotherapy of experimental brain tumors is greatly potentiated when combined with COX-2 inhibition. Based on our results, the clinically available drug parecoxib may be added to immunotherapy against human brain tumors. Furthermore, the discovery that IFN-γ plasma levels can be used to determine the ongoing in vivo immune response has translational potential. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer immunology, immunotherapy : CII
volume
61
issue
8
pages
1191 - 1199
publisher
Springer
external identifiers
  • wos:000306730700004
  • pmid:22213142
  • scopus:84865744728
ISSN
1432-0851
DOI
10.1007/s00262-011-1196-y
language
English
LU publication?
yes
id
fd35b8aa-739e-4866-be45-5bcb37c493db (old id 2336771)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22213142?dopt=Abstract
date added to LUP
2012-02-01 18:58:53
date last changed
2017-04-09 04:01:17
@article{fd35b8aa-739e-4866-be45-5bcb37c493db,
  abstract     = {Glioblastoma multiforme is the most common and aggressive malignant brain tumor in humans, and the prognosis is very poor despite conventional therapy. Immunotherapy represents a novel treatment approach, but the effect is often weakened by release of immune-suppressive molecules such as prostaglandins. In the current study, we investigated the effect of immunotherapy with irradiated interferon-γ (IFN-γ)-secreting tumor cells and administration of the selective cyclooxygease-2 (COX-2) inhibitor parecoxib as treatment of established rat brain tumors. COX-2 inhibition and immunotherapy significantly enhanced the long-term cure rate (81% survival) compared with immunotherapy alone (19% survival), and there was a significant increase in plasma IFN-γ levels in animals treated with the combined therapy, suggesting a systemic T helper 1 immune response. COX-2 inhibition alone, however, did neither induce cure nor prolonged survival. The tumor cells were identified as the major source of COX-2 both in vivo and in vitro, and unmodified tumor cells produced prostaglandin E(2) in vitro, while the IFN-γ expressing tumor cells secreted significantly lower levels. In conclusion, we show that immunotherapy of experimental brain tumors is greatly potentiated when combined with COX-2 inhibition. Based on our results, the clinically available drug parecoxib may be added to immunotherapy against human brain tumors. Furthermore, the discovery that IFN-γ plasma levels can be used to determine the ongoing in vivo immune response has translational potential.},
  author       = {Eberstål, Sofia and Badn, Wiaam and Fritzell, Sara and Esbjörnsson, Magnus and Darabi, Anna and Visse, Edward and Siesjö, Peter},
  issn         = {1432-0851},
  language     = {eng},
  number       = {8},
  pages        = {1191--1199},
  publisher    = {Springer},
  series       = {Cancer immunology, immunotherapy : CII},
  title        = {Inhibition of cyclooxygenase-2 enhances immunotherapy against experimental brain tumors.},
  url          = {http://dx.doi.org/10.1007/s00262-011-1196-y},
  volume       = {61},
  year         = {2012},
}