Immune System-Related Changes in Preclinical GL261 Glioblastoma under TMZ Treatment: Explaining MRSI-Based Nosological Imaging Findings with RT-PCR Analyses
Abstract
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. GL261 GB Preclinical Model Generation and Treatment
2.2. In Vivo MRI and MRSI Studies
2.2.1. MRI Studies
2.2.2. MRSI Studies
2.2.3. MRI and MRSI Processing and Post-Processing
- Tumour volume calculation
- Brain MRSI post-processing and machine learning strategies
2.2.4. Tumour Responding index (TRI) Calculations
2.3. Animal Euthanasia
2.4. RNA Isolation, cDNA Synthesis and qPCR
2.5. Statistical Analysis
3. Results
3.1. Follow up of GL261 Tumour-Bearing Mice and Endpoint Criteria
3.2. Microglia/Macrophage Global Population, As Well As M1 and M2 Subtypes, Are Increased in IMS-TMZ-Treated Tumours
3.3. Assessing Different Macrophage Population Subtypes Regarding Global GAMs Values
3.4. PD-L1 Gene Is Highly Expressed in IMS-TMZ-Treated Tumours, and These Increases May Be Correlated with the Polarisation State of Microglia/Macrophage Population
4. Discussion
4.1. Immune System Populations Change during Response to Therapy
4.2. Not All GAMs Are Equal (I): Polarisation of Microglia/Macrophages and Its Role in Therapy Response in GB
4.3. Not All GAMs Are Equal (II): The Polarisation Status of Microglia/Macrophages Affects Their Metabolomic Pattern
4.4. PD-L1 Gene Expression in GL261 GB
4.5. Wrap-up: Incoporating the Measured Gene Expression Results into the Explanation of the Oscillatory Behaviour of the MRSI-Based Biomarker of Response
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Relative Expression | |||||||
---|---|---|---|---|---|---|---|
F4/80 *** | Nos2 *** | CD206 ** | PD-L1 *** | M1/GAMs | M2/GAMs ** | M1/M2 * | |
IMS-TMZ-treated | 0.71 ± 0.32 | 0.05 ± 0.03 | 0.23 ± 0.09 | 1.07 ± 0.34 | 0.07 ± 0.02 | 0.35 ± 0.16 | 0.26 ± 0.16 |
IMS-vehicle treated | 0.18 ± 0.08 | 0.01 ± 0.01 | 0.13 ± 0.06 | 0.46 ± 0.16 | 0.08 ± 0.05 | 0.84 ± 0.34 | 0.11 ± 0.09 |
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Calero-Pérez, P.; Wu, S.; Arús, C.; Candiota, A.P. Immune System-Related Changes in Preclinical GL261 Glioblastoma under TMZ Treatment: Explaining MRSI-Based Nosological Imaging Findings with RT-PCR Analyses. Cancers 2021, 13, 2663. https://doi.org/10.3390/cancers13112663
Calero-Pérez P, Wu S, Arús C, Candiota AP. Immune System-Related Changes in Preclinical GL261 Glioblastoma under TMZ Treatment: Explaining MRSI-Based Nosological Imaging Findings with RT-PCR Analyses. Cancers. 2021; 13(11):2663. https://doi.org/10.3390/cancers13112663
Chicago/Turabian StyleCalero-Pérez, Pilar, Shuang Wu, Carles Arús, and Ana Paula Candiota. 2021. "Immune System-Related Changes in Preclinical GL261 Glioblastoma under TMZ Treatment: Explaining MRSI-Based Nosological Imaging Findings with RT-PCR Analyses" Cancers 13, no. 11: 2663. https://doi.org/10.3390/cancers13112663
APA StyleCalero-Pérez, P., Wu, S., Arús, C., & Candiota, A. P. (2021). Immune System-Related Changes in Preclinical GL261 Glioblastoma under TMZ Treatment: Explaining MRSI-Based Nosological Imaging Findings with RT-PCR Analyses. Cancers, 13(11), 2663. https://doi.org/10.3390/cancers13112663