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1.
Cancer Med ; 11(13): 2711-2726, 2022 07.
Article in English | MEDLINE | ID: covidwho-1919249

ABSTRACT

Recent evidence suggested that the mRNA vaccine has been effective for many tumors, but its progress in gliomas was slow. In this study, we screened potential tumor antigens and suitable populations for mRNA vaccine to develop mRNA vaccine for glioma. We integrated the normalized RNA sequencing expression data and somatic mutation data from TCGA-GBM, TCGA-LGG, and CGGA datasets. Putative antigens in glioma were identified by selecting highly mutated genes with intimate correlation with clinical survival and immune infiltration. An unsupervised partition around medoids algorithm was utilized to stably cluster the patients into five different immune subtypes. Among them, IS1/2 was cold tumor with low tumor mutation burden (TMB), immunogenic cell death (ICDs), and immune checkpoints (ICPs), and IS4/5 was hot tumor with high TMB, ICDs, and ICPs. Monocle3 package was used to evaluate the immune status similarity and evolution in glioma, which identified cluster IS2A/2B within IS2 subtype to be more suitable vaccination receivers. Weighted gene co-expression network analysis identified five hub immune genes as the biomarkers of patients' immune status in glioma. In conclusion, NAT1, FRRS1, GTF2H2C, BRCA2, GRAP, NR5A2, ABCB4, ZNF90, ERCC6L, and ZNF813 are potential antigens suitable for glioma mRNA vaccine. IS1/2A/2B are suitable for mRNA vaccination.


Subject(s)
Brain Neoplasms , Glioma , Antigens, Neoplasm/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Brain Neoplasms/pathology , Glioma/pathology , Humans , Prognosis , RNA, Messenger/genetics , Vaccines, Synthetic , mRNA Vaccines
2.
Front Immunol ; 12: 679425, 2021.
Article in English | MEDLINE | ID: covidwho-1344264

ABSTRACT

Gliomas are the most common primary brain tumors in adults. Despite the fact that they are relatively rare, they cause significant morbidity and mortality. High-grade gliomas or glioblastomas are rapidly progressing tumors with a very poor prognosis. The presence of an intrinsic immune system in the central nervous system is now more accepted. During the last decade, there has been no major progress in glioma therapy. The lack of effective treatment for gliomas can be explained by the strategies that cancer cells use to escape the immune system. This being said, immunotherapy, which involves blockade of immune checkpoint inhibitors, has improved patients' survival in different cancer types. This novel cancer therapy appears to be one of the most promising approaches. In the present study, we will start with a review of the general concept of immune response within the brain and glioma microenvironment. Then, we will try to decipher the role of various immune checkpoint inhibitors within the glioma microenvironment. Finally, we will discuss some promising therapeutic pathways, including immune checkpoint blockade and the body's effective anti-glioma immune response.


Subject(s)
Brain Neoplasms/drug therapy , Brain Neoplasms/pathology , Glioma/drug therapy , Glioma/pathology , Immune Checkpoint Inhibitors/therapeutic use , Tumor Microenvironment/drug effects , Biomarkers, Tumor , Brain/drug effects , Brain/immunology , Brain/metabolism , Brain/pathology , Brain Neoplasms/etiology , Brain Neoplasms/mortality , Disease Susceptibility , Glioma/etiology , Glioma/mortality , Humans , Immune Checkpoint Inhibitors/administration & dosage , Immune Checkpoint Inhibitors/adverse effects , Immune Checkpoint Proteins/genetics , Immune Checkpoint Proteins/metabolism , Molecular Targeted Therapy , Prognosis , Treatment Outcome , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology
3.
Cell Rep ; 33(3): 108286, 2020 10 20.
Article in English | MEDLINE | ID: covidwho-880155

ABSTRACT

Diffuse intrinsic pontine glioma (DIPG) is an incurable brain tumor of childhood characterized by histone mutations at lysine 27, which results in epigenomic dysregulation. There has been a failure to develop effective treatment for this tumor. Using a combined RNAi and chemical screen targeting epigenomic regulators, we identify the polycomb repressive complex 1 (PRC1) component BMI1 as a critical factor for DIPG tumor maintenance in vivo. BMI1 chromatin occupancy is enriched at genes associated with differentiation and tumor suppressors in DIPG cells. Inhibition of BMI1 decreases cell self-renewal and attenuates tumor growth due to induction of senescence. Prolonged BMI1 inhibition induces a senescence-associated secretory phenotype, which promotes tumor recurrence. Clearance of senescent cells using BH3 protein mimetics co-operates with BMI1 inhibition to enhance tumor cell killing in vivo.


Subject(s)
Aging/genetics , Diffuse Intrinsic Pontine Glioma/genetics , Polycomb Repressive Complex 1/metabolism , Astrocytoma/genetics , Brain Stem Neoplasms/drug therapy , Brain Stem Neoplasms/genetics , Cell Differentiation/genetics , Cell Line, Tumor , Cell Proliferation/drug effects , Child , Child, Preschool , Chromatin/genetics , Diffuse Intrinsic Pontine Glioma/drug therapy , Diffuse Intrinsic Pontine Glioma/metabolism , Epigenomics , Female , Glioma/drug therapy , Glioma/genetics , Glioma/pathology , Histones/metabolism , Humans , Lysine/metabolism , Male , Mutation , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/genetics , Polycomb Repressive Complex 1/antagonists & inhibitors , Polycomb Repressive Complex 1/genetics
5.
World Neurosurg ; 140: 46-48, 2020 08.
Article in English | MEDLINE | ID: covidwho-596185

ABSTRACT

BACKGROUND: Reports on neurologic manifestations of coronavirus disease 2019 (COVID-19) have attracted broad attention. We present an unusual case of COVID-19-associated encephalitis mimicking a glial tumor. CASE DESCRIPTION: A 35-year-old woman presented with headache and seizures. T2 fluid-attenuated inverse recovery imaging showed hyperintensities in the left temporal lobe. Magnetic resonance spectroscopy showed an elevated choline peak. Imaging findings were suggestive of high-grade glioma. Antiepileptic medication failed to achieve seizure control. A left anterior temporal lobectomy was performed. The patient had no postoperative deficits, and her symptoms completely improved. Histologic examination revealed encephalitis. Postoperatively, our patient tested positive for COVID-19. CONCLUSIONS: Our case raises awareness of neurologic manifestations of the disease and their potential to mimic glial tumors. For prompt diagnosis and prevention of transmission, clinicians should consider COVID-19 in patients with similar presentation.


Subject(s)
Betacoronavirus/pathogenicity , Coronavirus Infections/complications , Diagnosis, Differential , Encephalitis/virology , Glioma/diagnosis , Pneumonia, Viral/complications , Adult , COVID-19 , Coronavirus Infections/pathology , Encephalitis/diagnosis , Encephalitis/pathology , Female , Glioma/pathology , Headache/virology , Humans , Pandemics , Pneumonia, Viral/pathology , SARS-CoV-2 , Seizures/pathology , Seizures/virology , Temporal Lobe/pathology , Temporal Lobe/virology
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