scholarly journals Immune Profiling of Syngeneic Murine and Patient GBMs for Effective Translation of Immunotherapies

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 491
Author(s):  
Jasneet Kaur Khalsa ◽  
Khalid Shah

Immunotherapy for brain tumors remains elusive, unlike many other cancer types for which it is one of the most promising therapeutic options. Recent studies have comprehensively profiled the immune-landscape of the highly malignant brain tumor, glioblastoma (GBM) in patients and identified novel immune-modulatory targets. However, given that pre-clinical exploration of potential novel therapeutics is primarily performed in immune-competent mice, it is vital to compare the immune-profiling data obtained from syngeneic mouse GBM models with GBM patient samples. This will pave the way for utilizing appropriate clinically relevant mouse GBM models for evaluating novel immune-therapies in pre-clinical settings. Recent brain tumor immune-profiling studies using state-of-the-art time of flight cytometry (CyTOF) analysis compared different human and mouse GBM types and reported immunological distinctions amongst these mouse models. These studies also contrast the immune phenotype of brain tumor patients with commonly used pre-clinical immune-competent mouse models. In this perspective, we provide the outcomes of very recent brain tumor immune-profiling studies and their implications on designing and translating unique, tumor-subtype specific therapeutics.

2021 ◽  
Vol 1 (2) ◽  
Author(s):  
Abhishek Chaturbedi

Brain tumors are complex entities with facts as numerous as stars in our sky, uncountable. They exist and thus every treating physician and surgeon happens to come across it. We try to put major contemporary practices and facts in a single bucket from learned skills of neurology and oncology tradition and things we received as feedback from our patients in clinical settings. Purpose of this work is to refresh your knowledge and preparedness for seeing patients with brain cancer. Brain tumors are molecularly heterogeneous and their features depend upon size, site, and genetic make-up of tumor, aggressive growth, and adjacent structures. Complications and their management are very challenging. This article will comfortably sail you through various aspects of management of brain cancers.


2019 ◽  
Vol 21 (10) ◽  
pp. 1297-1309 ◽  
Author(s):  
Denise D Correa ◽  
Jaya Satagopan ◽  
Axel Martin ◽  
Erica Braun ◽  
Maria Kryza-Lacombe ◽  
...  

AbstractBackgroundPatients with brain tumors treated with radiotherapy (RT) and chemotherapy (CT) often experience cognitive dysfunction. We reported that single nucleotide polymorphisms (SNPs) in the APOE, COMT, and BDNF genes may influence cognition in brain tumor patients. In this study, we assessed whether genes associated with late-onset Alzheimer’s disease (LOAD), inflammation, cholesterol transport, dopamine and myelin regulation, and DNA repair may influence cognitive outcome in this population.MethodsOne hundred and fifty brain tumor patients treated with RT ± CT or CT alone completed a neurocognitive assessment and provided a blood sample for genotyping. We genotyped genes/SNPs in these pathways: (i) LOAD risk/inflammation/cholesterol transport, (ii) dopamine regulation, (iii) myelin regulation, (iv) DNA repair, (v) blood–brain barrier disruption, (vi) cell cycle regulation, and (vii) response to oxidative stress. White matter (WM) abnormalities were rated on brain MRIs.ResultsMultivariable linear regression analysis with Bayesian shrinkage estimation of SNP effects, adjusting for relevant demographic, disease, and treatment variables, indicated strong associations (posterior association summary [PAS] ≥ 0.95) among tests of attention, executive functions, and memory and 33 SNPs in genes involved in: LOAD/inflammation/cholesterol transport (eg, PDE7A, IL-6), dopamine regulation (eg, DRD1, COMT), myelin repair (eg, TCF4), DNA repair (eg, RAD51), cell cycle regulation (eg, SESN1), and response to oxidative stress (eg, GSTP1). The SNPs were not significantly associated with WM abnormalities.ConclusionThis novel study suggests that polymorphisms in genes involved in aging and inflammation, dopamine, myelin and cell cycle regulation, and DNA repair and response to oxidative stress may be associated with cognitive outcome in patients with brain tumors.


2021 ◽  
Vol 2 (1) ◽  
pp. 100290
Author(s):  
Katharina M. Eyme ◽  
Litia Carvalho ◽  
Christian E. Badr

2021 ◽  
Author(s):  
Frederik Grosse ◽  
Florian Wedel ◽  
Ulrich-Wilhelm Thomale ◽  
Ingo Steffen ◽  
Arend Koch ◽  
...  

Abstract Background MRI has shortcomings in differentiation between tumor tissue and post-therapeutic changes in pretreated brain tumor patients. Patients We assessed 22 static FET-PET/CT-scans of 17 pediatric patients (median age 12 years, range 2–16 years, ependymoma n=4, medulloblastoma n=4, low-grade glioma n=6, high-grade glioma n=3, germ cell tumor n=1, choroid plexus tumor n=1, median follow-up: 112 months) with multimodal treatment. Method FET-PET/CT-scans were analyzed visually by 3 independent nuclear medicine physicians. Additionally quantitative FET-Uptake for each lesion was determined by calculating standardized uptake values (SUVmaxT/SUVmeanB, SUVmeanT/SUVmeanB). Histology or clinical follow-up served as reference. Results Static FET-PET/CT reliably distinguished between tumor tissue and post-therapeutic changes in 16 out of 17 patients. It identified correctly vital tumor tissue in 13 patients and post-therapeutic changes in 3 patients. SUV-based analyses were less sensitive than visual analyses. Except from a choroid plexus carcinoma, all tumor entities showed increased FET-uptake. Discussion Our study comprises a limited number of patients but results corroborate the ability of FET to detect different brain tumor entities in pediatric patients and discriminate between residual/recurrent tumor and post-therapeutic changes. Conclusions We observed a clear benefit from additional static FET-PET/CT-scans when conventional MRI identified equivocal lesions in pretreated pediatric brain tumor patients. These results warrant prospective studies that should include dynamic scans.


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