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Immunizations with unmodified tumor cells and simultaneous COX-2 inhibition eradicate malignant rat brain tumors and induce a long-lasting CD8(+) T cell memory.

Eberstål, Sofia LU ; Fritzell, Sara LU ; Sandén, Emma LU ; Visse, Edward LU ; Darabi, Anna LU and Siesjö, Peter LU (2014) In Journal of Neuroimmunology 274(1-2). p.161-167
Abstract
Malignant brain tumors induce pronounced immunosuppression, which diminishes immune responses generated by immunotherapy. Here we report that peripheral immunotherapy, using irradiated unmodified whole tumor cells, and systemic cyclooxygenase-2 inhibition induce cure in glioma-bearing rats (60% cure rate), whereas neither monotherapy was sufficient to cure any animal. Moreover, the combined therapy protected against secondary tumor challenges (89% cure rate) and the secondary immune response was correlated with increased plasma interferon-gamma levels and CD8(+) T cells systemically and intratumorally. In conclusion, we demonstrate that cyclooxygenase-2 inhibition is sufficient to render unmodified tumor cells immunogenic in immunotherapy... (More)
Malignant brain tumors induce pronounced immunosuppression, which diminishes immune responses generated by immunotherapy. Here we report that peripheral immunotherapy, using irradiated unmodified whole tumor cells, and systemic cyclooxygenase-2 inhibition induce cure in glioma-bearing rats (60% cure rate), whereas neither monotherapy was sufficient to cure any animal. Moreover, the combined therapy protected against secondary tumor challenges (89% cure rate) and the secondary immune response was correlated with increased plasma interferon-gamma levels and CD8(+) T cells systemically and intratumorally. In conclusion, we demonstrate that cyclooxygenase-2 inhibition is sufficient to render unmodified tumor cells immunogenic in immunotherapy of experimental brain tumors. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Neuroimmunology
volume
274
issue
1-2
pages
161 - 167
publisher
Elsevier
external identifiers
  • pmid:25022336
  • wos:000342871600020
  • scopus:84906939281
ISSN
1872-8421
DOI
10.1016/j.jneuroim.2014.06.019
language
English
LU publication?
yes
id
eaaced2f-8f21-4918-9f7c-aa85d4ea537e (old id 4582364)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25022336?dopt=Abstract
date added to LUP
2014-08-07 22:58:31
date last changed
2017-01-01 03:17:15
@article{eaaced2f-8f21-4918-9f7c-aa85d4ea537e,
  abstract     = {Malignant brain tumors induce pronounced immunosuppression, which diminishes immune responses generated by immunotherapy. Here we report that peripheral immunotherapy, using irradiated unmodified whole tumor cells, and systemic cyclooxygenase-2 inhibition induce cure in glioma-bearing rats (60% cure rate), whereas neither monotherapy was sufficient to cure any animal. Moreover, the combined therapy protected against secondary tumor challenges (89% cure rate) and the secondary immune response was correlated with increased plasma interferon-gamma levels and CD8(+) T cells systemically and intratumorally. In conclusion, we demonstrate that cyclooxygenase-2 inhibition is sufficient to render unmodified tumor cells immunogenic in immunotherapy of experimental brain tumors.},
  author       = {Eberstål, Sofia and Fritzell, Sara and Sandén, Emma and Visse, Edward and Darabi, Anna and Siesjö, Peter},
  issn         = {1872-8421},
  language     = {eng},
  number       = {1-2},
  pages        = {161--167},
  publisher    = {Elsevier},
  series       = {Journal of Neuroimmunology},
  title        = {Immunizations with unmodified tumor cells and simultaneous COX-2 inhibition eradicate malignant rat brain tumors and induce a long-lasting CD8(+) T cell memory.},
  url          = {http://dx.doi.org/10.1016/j.jneuroim.2014.06.019},
  volume       = {274},
  year         = {2014},
}