class II transactivator; glioblastoma; natural killer cells; tumor microenvironment; tumor-associated macrophages; tumor-infiltrating lymphocytes; Oncology; Cancer Research
Abstract :
[en] Background: The major histocompatibility complex type II is downregulated in glioblastoma (GB) due to the silencing of the major transcriptional regulator class II transactivator (CIITA). We investigated the pro-immunogenic potential of CIITA overexpression in mouse and human GB. Methods: The intracerebral growth of wildtype GL261-WT cells was assessed following contralateral injection of GL261-CIITA cells or flank injections with GL261-WT or GL261-CIITA cells. Splenocytes obtained from mice implanted intracerebrally with GL261-WT, GL261-CIITA cells or phosphate buffered saline (PBS) were transferred to other mice and subsequently implanted intracerebrally with GL261-WT. Human GB cells and (syngeneic) GB-infiltrating immune cells were isolated from surgical samples and co-cultured with GB cells expressing CIITA or not, followed by RT-qPCR assessment of the expression of key immune regulators. Results: Intracerebral vaccination of GL261-CIITA significantly reduced the subsequent growth of GL261-WT cells implanted contralaterally. Vaccination with GL261-WT or -CIITA subcutaneously, however, equivalently retarded the intracerebral growth of GL261 cells. Adoptive cell transfer experiments showed a similar antitumor potential of lymphocytes harvested from mice implanted intracerebrally with GL261-WT or -CIITA. Human GB-infiltrating myeloid cells and lymphocytes were not activated when cultured with CIITA-expressing GB cells. Tumor-infiltrating NK cells remained mostly inactivated when in co-culture with GB cells, regardless of CIITA. Conclusion: these results question the therapeutic potential of CIITA-mediated immunotherapy in glioblastoma.
Disciplines :
Genetics & genetic processes
Author, co-author :
Tan, A. Katherine; Department of Translational Neuroscience, University Medical Center Utrecht (UMCU) Brain Center, Utrecht University, Utrecht, Netherlands
Henry, Aurélie ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Génétique humaine
Goffart, Nicolas ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biochimie et physiologie générales, et biochimie humaine
van Logtestijn, Sofie; Department of Translational Neuroscience, University Medical Center Utrecht (UMCU) Brain Center, Utrecht University, Utrecht, Netherlands
Bours, Vincent ; Université de Liège - ULiège > GIGA > GIGA Cancer - Human Genetics
Hol, Elly M. ; Department of Translational Neuroscience, University Medical Center Utrecht (UMCU) Brain Center, Utrecht University, Utrecht, Netherlands
Robe, Pierre ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Génétique humaine ; Department of Translational Neuroscience, University Medical Center Utrecht (UMCU) Brain Center, Utrecht University, Utrecht, Netherlands ; Department of Neurosurgery, University Medical Center Utrecht (UMCU) Brain Center, Utrecht University, Utrecht, Netherlands
Language :
English
Title :
Limited Effects of Class II Transactivator-Based Immunotherapy in Murine and Human Glioblastoma
Publication date :
2024
Journal title :
Cancers
eISSN :
2072-6694
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI)
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
Funding text :
This research was funded by Fonds de la Recherche Scientifique of Belgium grants (8.4628.16, 7.4639.17) and a Ton & Patricia Bohnenn Fund for Neuro-Oncology Research grant. Ton & Patricia Bohnenn Fund for Neuro-Oncology Research
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