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The effect of locally delivered cisplatin is dependent on an intact immune function in an experimental glioma model

Enríquez Pérez, Julio LU orcid ; Fritzell, Sara LU ; Kopecky, Jan LU orcid ; Visse, Edward LU ; Darabi, Anna LU and Siesjö, Peter LU orcid (2019) In Scientific Reports 9(1).
Abstract


Several chemotherapeutic drugs are now considered to exert anti-tumour effects, by inducing an immune-promoting inflammatory response. Cisplatin is a potent chemotherapeutic agent used in standard medulloblastoma but not glioblastoma protocols. There is no clear explanation for the differences in clinical efficacy of cisplatin between medulloblastomas and glioblastomas, despite the fact that cisplatin is effective in vitro against the latter. Systemic toxicity is often dose limiting but could tentatively be reduced by intratumoral administration. We found that intratumoral cisplatin can cure GL261 glioma-bearing C57BL/6 mice and this effect was abolished in GL261-bearing... (More)


Several chemotherapeutic drugs are now considered to exert anti-tumour effects, by inducing an immune-promoting inflammatory response. Cisplatin is a potent chemotherapeutic agent used in standard medulloblastoma but not glioblastoma protocols. There is no clear explanation for the differences in clinical efficacy of cisplatin between medulloblastomas and glioblastomas, despite the fact that cisplatin is effective in vitro against the latter. Systemic toxicity is often dose limiting but could tentatively be reduced by intratumoral administration. We found that intratumoral cisplatin can cure GL261 glioma-bearing C57BL/6 mice and this effect was abolished in GL261-bearing NOD-scid IL2rγ
null
(NSG) mice. Contrary to previous results with intratumoral temozolomide cisplatin had no additive or synergistic effect with whole cell either GL261 wild-type or GM-CSF-transfected GL261 cells whole cell vaccine-based immunotherapy. While whole tumour cell immunizations increased CD8
+
T-cells and decreased F4/80
+
macrophages intratumorally, cisplatin had no effect on these cell populations. Taken together, our results demonstrate that intratumoral cisplatin treatment was effective with a narrow therapeutic window and may be an efficient approach for glioma or other brain tumour treatment.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
9
issue
1
article number
5632
publisher
Nature Publishing Group
external identifiers
  • scopus:85063983413
  • pmid:30948731
ISSN
2045-2322
DOI
10.1038/s41598-019-42001-7
project
Immunological aspects of intratumoral chemotherapy and immunotherapy in malignant brain tumors
language
English
LU publication?
yes
id
4a104fe1-f10c-4255-a61b-947eb3c32da2
date added to LUP
2019-04-24 09:02:09
date last changed
2024-05-14 06:28:12
@article{4a104fe1-f10c-4255-a61b-947eb3c32da2,
  abstract     = {{<p><br>
                                                         Several chemotherapeutic drugs are now considered to exert anti-tumour effects, by inducing an immune-promoting inflammatory response. Cisplatin is a potent chemotherapeutic agent used in standard medulloblastoma but not glioblastoma protocols. There is no clear explanation for the differences in clinical efficacy of cisplatin between medulloblastomas and glioblastomas, despite the fact that cisplatin is effective in vitro against the latter. Systemic toxicity is often dose limiting but could tentatively be reduced by intratumoral administration. We found that intratumoral cisplatin can cure GL261 glioma-bearing C57BL/6 mice and this effect was abolished in GL261-bearing NOD-scid IL2rγ                             <br>
                            <sup>null</sup><br>
                                                          (NSG) mice. Contrary to previous results with intratumoral temozolomide cisplatin had no additive or synergistic effect with whole cell either GL261 wild-type or GM-CSF-transfected GL261 cells whole cell vaccine-based immunotherapy. While whole tumour cell immunizations increased CD8                             <br>
                            <sup>+</sup><br>
                                                          T-cells and decreased F4/80                             <br>
                            <sup>+</sup><br>
                                                          macrophages intratumorally, cisplatin had no effect on these cell populations. Taken together, our results demonstrate that intratumoral cisplatin treatment was effective with a narrow therapeutic window and may be an efficient approach for glioma or other brain tumour treatment.                         <br>
                        </p>}},
  author       = {{Enríquez Pérez, Julio and Fritzell, Sara and Kopecky, Jan and Visse, Edward and Darabi, Anna and Siesjö, Peter}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  month        = {{04}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{The effect of locally delivered cisplatin is dependent on an intact immune function in an experimental glioma model}},
  url          = {{http://dx.doi.org/10.1038/s41598-019-42001-7}},
  doi          = {{10.1038/s41598-019-42001-7}},
  volume       = {{9}},
  year         = {{2019}},
}