Anti-PD-1 immunotherapy in preclinical GL261 glioblastoma : influence of therapeutic parameters and noninvasive response biomarker assessment with MRSI-based approaches
Wu, Shuang (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Calero-Perez, Pilar (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Arús i Caraltó, Carles (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Candiota Silveira, Ana Paula (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")

Date:	2020
Abstract:	Glioblastomas (GBs) are malignant brain tumours with poor prognosis even after aggressive therapy. Programmed cell death-1 (PD-1) immune checkpoint blockade is a promising strategy in many types of cancer, but its therapeutic effects in GB remain low and associated with immune infiltration. Previous work suggests that oscillations of magnetic resonance spectroscopic imaging (MRSI)-based response pattern with chemotherapy could act as a biomarker of efficient immune system attack onto GBs. The presence of such oscillations with other monotherapies such as anti-PD-1 would reinforce its monitoring potential. Here, we confirm that the oscillatory behaviour of the response biomarker is also detected in mice treated with anti PD-1 immunotherapy both in combination with temozolomide and as monotherapy. This indicates that the spectral pattern changes observed during therapy response are shared by different therapeutic strategies, provided the host immune system is elicited and able to productively attack tumour cells. Moreover, the participation of the immune system in response is also supported by the rate of cured animals observed with different therapeutic strategies (in the range of 50-100% depending on the treatment), which also held long-term immune memory against tumour cells re-challenge. Taken together, our findings open the way for a translational use of the MRSI-based biomarker in patient-tailored GB therapy, including immunotherapy, for which reliable non-invasive biomarkers are still missing.
Grants:	Ministerio de Economía y Competitividad SAF2014-52332-R Ministerio de Sanidad y Consumo CB06/01/0010 European Commission 777222
Note:	Altres ajuts: UAB Predoctoral training programme (14ª Convocatoria PIF-19612, predoctoral fellowships for P.C.-P.)
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 ; Checkpoint inhibitors ; TMZ ; Therapy response biomarker ; Magnetic resonance spectroscopic imaging ; Long-term immune memory
Published in:	International journal of molecular sciences, Vol. 21, Issue 22 (November 2020) , art. 8775, ISSN 1422-0067

DOI: 10.3390/ijms21228775
PMID: 33233585

24 p, 3.3 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)
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