Understanding the Effect of Aspartate Hydroxylase Inhibition On T Cell-Mediated Immunity Using Single-Cell RNA Sequencing
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F23%3A10467565" target="_blank" >RIV/00216208:11310/23:10467565 - isvavai.cz</a>
Výsledek na webu
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DOI - Digital Object Identifier
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Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Understanding the Effect of Aspartate Hydroxylase Inhibition On T Cell-Mediated Immunity Using Single-Cell RNA Sequencing
Popis výsledku v původním jazyce
Overexpression of aspartate β-hydroxylase (ASPH) was found in 70-90% of solid tumors but is negligible in normal tissues. Increased ASPH contributes to tumor cell proliferation, migration, and invasion but can also affect immune cells. In this study, we showed that ASPH inhibition with the small molecule inhibitor MO-I-1151 enhanced the anti-tumor effect stimulated by DNA immunization and activated an adaptive immunity mediated by CD4+ and CD8+ T cells. To reveal the mechanisms involved, we performed single-cell RNA sequencing with CD45+ tumor-infiltrating cells. Seurat and QIAGEN Ingenuity Pathway Analysis showed that inhibition of ASPH induced differences in infiltration with immune cells and cytokine/chemokine profiles of T cells in tumors of immunized mice. These results suggest a suppressive effect of ASPH on anti-tumor adaptive immunity that could be eliminated by ASPH inhibition.
Název v anglickém jazyce
Understanding the Effect of Aspartate Hydroxylase Inhibition On T Cell-Mediated Immunity Using Single-Cell RNA Sequencing
Popis výsledku anglicky
Overexpression of aspartate β-hydroxylase (ASPH) was found in 70-90% of solid tumors but is negligible in normal tissues. Increased ASPH contributes to tumor cell proliferation, migration, and invasion but can also affect immune cells. In this study, we showed that ASPH inhibition with the small molecule inhibitor MO-I-1151 enhanced the anti-tumor effect stimulated by DNA immunization and activated an adaptive immunity mediated by CD4+ and CD8+ T cells. To reveal the mechanisms involved, we performed single-cell RNA sequencing with CD45+ tumor-infiltrating cells. Seurat and QIAGEN Ingenuity Pathway Analysis showed that inhibition of ASPH induced differences in infiltration with immune cells and cytokine/chemokine profiles of T cells in tumors of immunized mice. These results suggest a suppressive effect of ASPH on anti-tumor adaptive immunity that could be eliminated by ASPH inhibition.
Klasifikace
Druh
O - Ostatní výsledky
CEP obor
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OECD FORD obor
30102 - Immunology
Návaznosti výsledku
Projekt
Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>S - Specificky vyzkum na vysokych skolach
Ostatní
Rok uplatnění
2023
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů