Immune system-related changes in preclinical GL261 glioblastoma under TMZ treatment : Explaining MRSI-based nosological imaging findings with RT-PCR analyses
Calero-Perez, Pilar (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Wu, Shuang (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Arús i Caraltó, Carles (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Candiota Silveira, Ana Paula (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")

Date:	2021
Abstract:	Glioblastomas (GB) are brain tumours with poor prognosis even after aggressive therapy. Previous work suggests that magnetic resonance spectroscopic imaging (MRSI) could act as a biomarker of efficient immune system attack onto GB, presenting oscillatory changes. Glioma-associated microglia/macrophages (GAMs) constitute the most abundant non-tumour cell type within the GB and can be polarised into anti-tumour (M1) or pro-tumour (M2) phenotypes. One of the mechanisms to mediate immunosuppression in brain tumours is the interaction between programmed cell death-1 ligand 1 (PD-L1) and programmed cell death-1 receptor (PD-1). We evaluated the subpopulations of GAMs in responding and control GB tumours to correlate PD-L1 expression to GAM polarisation in order to explain/validate MRSI-detected findings. Mice were evaluated by MRI/MRSI to assess the extent of response to treatment and with qPCR for GAMs M1 and M2 polarisation analyses. M1/M2 ratios and PD-L1 expression were higher in treated compared to control tumours. Furthermore, PD-L1 expression was positively correlated with the M1/M2 ratio. The oscillatory change in the GAMs prevailing population could be one of the key causes for the differential MRSI-detected pattern, allowing this to act as immune system activity biomarker in future work.
Grants:	Ministerio de Economía y Competitividad SAF2014-52332-R European Commission 813120 European Commission 777222 Ministerio de Sanidad y Consumo CB06/01/0010 Agència de Gestió d'Ajuts Universitaris i de Recerca 2018/XARDI-00016
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Glioblastoma ; Orthotopic immunocompetent tumours ; Immune-enhancing metronomic schedule ; TMZ ; Magnetic resonance spectroscopic imaging ; Immune system activity imaging biomarker ; Cancer immune cycle ; Glioma-associated microglia/macrophages ; PD-L1
Published in:	Cancers, Vol. 13, Issue 11 (June 2021) , art. 2663, ISSN 2072-6694

DOI: 10.3390/cancers13112663
PMID: 34071393

19 p, 1.3 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles