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
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:
https://lup.lub.lu.se/record/2336771
- author
- Eberstål, Sofia
LU
; Badn, Wiaam
LU
; Fritzell, Sara
LU
; Esbjörnsson, Magnus
; Darabi, Anna
LU
; Visse, Edward
LU
and Siesjö, Peter
LU
- organization
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Cancer immunology, immunotherapy
- volume
- 61
- issue
- 8
- pages
- 1191 - 1199
- publisher
- Springer
- external identifiers
-
- wos:000306730700004
- pmid:22213142
- scopus:84865744728
- pmid:22213142
- 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
- 2016-04-01 14:11:08
- date last changed
- 2022-04-06 17:17:04
@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}},
title = {{Inhibition of cyclooxygenase-2 enhances immunotherapy against experimental brain tumors.}},
url = {{https://lup.lub.lu.se/search/files/3830772/2370051.pdf}},
doi = {{10.1007/s00262-011-1196-y}},
volume = {{61}},
year = {{2012}},
}