Affiliation:
1. State Key Laboratory of Medicinal Chemical Biology, College of Pharmacy and Tianjin Key Laboratory of Molecular Drug Research Nankai University Tianjin China
2. School of Integrative Medicine Tianjin University of Traditional Chinese Medicine Tianjin China
3. Department of Pathology Characteristic Medical Center of The Chinese People's Armed Police Force Tianjin China
Abstract
AbstractDue to the existence of the blood–brain barrier in glioma, traditional drug therapy has a poor therapeutic outcome. Emerging immunotherapy has been shown to have satisfactory therapeutic effects in solid tumors, and it is clinically instructive to explore the possibility of immunotherapy in glioma. We performed a retrospective analysis of RNA‐seq data and clinical information in 1027 glioma patients, utilizing machine learning to explore the relationship between tyrosine metabolizing enzymes and clinical characteristics. In addition, we also assessed the role of tyrosine metabolizing enzymes in the immune microenvironment including immune infiltration and immune evasion. Highly expressed tyrosine metabolizing enzymes 4‐hydroxyphenylpyruvate dioxygenase, homogentisate 1,2‐dioxygenase, and fumarylacetoacetate hydrolase not only promote the malignant phenotype of glioma but are also closely related to poor prognosis. The expression of tyrosine metabolizing enzymes could distinguish the malignancy degree of glioma. More importantly, tyrosine metabolizing enzymes regulate the adaptive immune process in glioma. Mechanistically, multiple metabolic enzymes remodel fumarate metabolism, promote α‐ketoglutarate production, induce programmed death‐ligand 1 expression, and help glioma evade immune surveillance. Our data suggest that the metabolic subclass driven by tyrosine metabolism provides promising targets for the immunotherapy of glioma.
Funder
National Natural Science Foundation of China
Natural Science Foundation of Tianjin City
Cited by
1 articles.
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