Glioblastoma Susceptibility to SARS-CoV-2: Analysis of Cancer Stem Cells and Immune Tumor Microenvironment on Human Brain, Patient-Derived Tumors, and Organoid Models
Clinical Neurosurgery
; 69(Supplement 1):140, 2023.
Article
in English
| EMBASE | ID: covidwho-2314736
ABSTRACT
INTRODUCTION:
Glioblastoma (GBM) is the most common and deadliest primary brain tumor, characterized by chemoradiation resistance and an immunosuppressive tumor microenvironment (TME). SARS-CoV-2, the COVID-19 virus, produces a significant proinflammatory response and a spectrum of clinical presentations after central nervous system infection. METHOD(S) Patient-derived GBM tissue, primary cell lines, and organoids were analyzed with immunohistochemistry and pixel-line intensity quantification. Data from tumor-bulk and single-cell transcriptomics served to describe the cell-specific expression of SARS-CoV-2 receptors in GBM and its association with the immune TME phenotype. Normal brain and iPSC-derived organoids served as controls. RESULT(S) We demonstrate that patient-derivedGBMtissue and cell cultures express SARS-CoV2 entry factors such as ACE2, TMPRSS2, and NRP1. NRP1 expression was higher in GBM than in normal brains (p<0.05), where it plays a crucial role in SARS-CoV-2 infection. NRP1 was expressed in a cell-type and phenotype-specific manner and correlated with TME infiltration of immunosuppressive cells M2 macrophages (r = 0.229), regulatory T cells (r = 0.459), NK cells (r = -0.346), and endothelial cells (r = 0.288) (p < 0.05). Furthermore, gene ontology enrichment analysis showed that leukocyte migration and chemotaxis are among the top 5 biological functions mediated by NRP1 (p < 0.05). We found our GBM organoids recapitulate tumoral expression of SARSCoV- 2 entry factors, which varies based on distance from surface as surrogate of TME oxygenation (p < 0.05). CONCLUSION(S) GBM cancer cells and immune TME cells express SARS-CoV-2 entry factors. Glioblastoma organoids recapitulate this expression and allow for currently undergoing studies analyzing the effect of SARS-CoV-2 infection in GBM. Our findings suggest that SARSCoV- 2 could potentially target GBM, opening the door to future studies evaluating SARS-CoV-2-driven immune modulation.
adult; brain; cancer cell; cancer patient; cancer stem cell; cell culture; chemotaxis; conference abstract; controlled study; coronavirus disease 2019; endothelium cell; gene expression; gene ontology; glioblastoma; histopathology; human; human cell; human tissue; immunohistochemistry; immunomodulation; induced pluripotent stem cell; leukocyte migration; M2 macrophage; natural killer cell; nonhuman; organoid; oxygenation; primary cell line; protein expression; protein function; regulatory T lymphocyte; Severe acute respiratory syndrome coronavirus 2; single cell RNA seq; tumor microenvironment; angiotensin converting enzyme 2; endogenous compound; neuropilin 1; transmembrane protease serine 2
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Collection:
Databases of international organizations
Database:
EMBASE
Language:
English
Journal:
Clinical Neurosurgery
Year:
2023
Document Type:
Article
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