Facial reconstruction

Search LJMU Research Online

Browse Repository | Browse E-Theses

Anti-tumour immune response in GL261 glioblastoma generated by Temozolamide Immune-Enhancing Metronomic Schedule monitored with MRSI-based nosological images

Wu, S, Calero-Pérez, P, Villamañan, L, Arias-Ramos, N, Pumarola, M, Ortega Martorell, S, Julià-Sapé, M, Arús, C and Candiota, AP (2020) Anti-tumour immune response in GL261 glioblastoma generated by Temozolamide Immune-Enhancing Metronomic Schedule monitored with MRSI-based nosological images. NMR in Biomedicine. ISSN 0952-3480 (Accepted)

[img] Text
Anti-tumour immune response in GL261 glioblastoma generated by Temozolomide Immune-Enhancing Metronomic Schedule monitored with MRSI-based nosological images.pdf - Accepted Version
Restricted to Repository staff only until 11 January 2021.

Download (1MB)
[img] Text
Figures.pdf - Supplemental Material
Restricted to Repository staff only until 11 January 2021.

Download (1MB)
[img] Text
SupplementaryMaterial.pdf - Supplemental Material
Restricted to Repository staff only until 11 January 2021.

Download (2MB)

Abstract

Glioblastomas (GB) are brain tumours with poor prognosis even after aggressive therapy. Improvements in both therapeutic and follow-up strategies are urgently needed. In previous work we described an oscillatory pattern of response to Temozolomide (TMZ) using a standard administration protocol, detected through MRSI-based machine learning approaches. In the present work, we have introduced the Immune-Enhancing Metronomic Schedule (IMS) with an every 6-days TMZ administration at 60mg/kg, and investigated the consistence of such oscillatory behaviour.
A total of n=17 GL261 GB tumour-bearing C57BL/6j mice were studied with MRI/MRSI every 2 days, and the oscillatory behaviour (6.2±1.5 days period from the TMZ administration day) was confirmed during response. Furthermore, IMS-TMZ produced significant improvement in mice survival (22.5±3.0 days for controls vs 135.8±78.2 for TMZ-treated), outperforming standard TMZ treatment.
Histopathological correlation was investigated in selected tumour samples (n=6) analyzing control and responding fields. Significant differences were found for CD3+ cells (lymphocytes, 3.3±2.5 vs 4.8±2.9 respectively) and Iba-1 immunostained area (microglia/macrophages, 16.8±9.7% and 21.9±11.4% respectively).
Unexpectedly, during IMS-TMZ treatment, tumours from some mice (n=6) fully regressed and remained undetectable without further treatment for one month. These animals were considered “cured” and a GL261 re-challenge experiment performed, with no tumour reappearance in 5 out of 6 cases.
Heterogeneous therapy response outcomes were detected in tumour-bearing mice, and a selected group was investigated (n=3 non-responders, n=6 relapsing tumours, n=3 controls). PD-L1 content was found ca. 3-fold increased in the relapsing group when comparing with control and non-responding groups, suggesting that increased lymphocyte inhibition could be associated to IMS-TMZ failure. Overall, data suggest that host immune response has a relevant paper in therapy response/escape in GL261 tumours under IMS-TMZ therapy. This is associated to changes in the metabolomics pattern, oscillating every 6 days, in agreement with immune cycle length, which is being sampled by MRSI-derived nosological images.

Item Type: Article
Additional Information: This is the peer reviewed version of the following article: Wu, S, Calero‐Pérez, P, Villamañan, L, et al. Anti‐tumour immune response in GL261 glioblastoma generated by Temozolomide Immune‐Enhancing Metronomic Schedule monitored with MRSI‐based nosological images. NMR in Biomedicine. 2020;e4229 which has been published in final form at https://doi.org/10.1002/nbm.4229. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
Uncontrolled Keywords: 1103 Clinical Sciences, 0304 Medicinal and Biomolecular Chemistry, 0903 Biomedical Engineering
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions: Applied Mathematics
Publisher: Wiley
Date Deposited: 07 Nov 2019 11:52
Last Modified: 14 Jan 2020 09:15
URI: http://researchonline.ljmu.ac.uk/id/eprint/11715

Actions (login required)

View Item View Item