Date of Award
Reading, Language, and Literature
Dr. Sandeep Mittal
Gliomas are the most common brain tumor and glioblastoma multiforme (GBM) is the most common type of glioma observed in patients. Prognosis with late stage glioma and GBM is very poor even with recent advances in treatment. Along with treating the tumor, manners of bypassing the blood brain barrier and ensuring the tumor uptakes the treatment is necessary. Because the treatments can harm regular brain cells there is concern about the viability and toxic side effects of many treatments. With all of these challenges posed it is important to understand how glial tumors can be so recurring and difficult to treat. One method employed by the tumors is utilizing the kynurenine pathway of tryptophan metabolism to suppress the immune system and promote tumor proliferation. Tryptophan is brought in to the cell by L-amino acid transporter (LAT1) and catabolized in to tryptophan by indoleamine 2,3 dioxygenase I/II (IDO-1/IDO-2), tryptophan 2,3 dioxygenase (TDO-2), kynurenine-3-monoxygenase (KMO), and kynureninase (KYNU). Finally this kynurenine can interact with the aryl hydrocarbon receptor (AHR) to promote gene transcription that allows the tumor to further thrive. Immunohistochemical staining across all grades and types of gliomas reveals expression patterns for the enzymes involved in the tryptophan metabolism. The staining revealed high, near-ubiquitous expression for IDO-2, TDO-2, KYNU, and LAT-1. KMO and IDO-1 had staining in the majority of the tissues and AHR showed the least expression. A repeat of this experiment with more cases is required so that a statistical analysis may be done on the expression patterns for the proteins. The six proteins with high expression show promise as viable targets for immunotherapy but more in vitro and in vivo experiments are required to determine if they are feasible treatments.
Varadarajan, Kaushik, "Qualitatively Assessing the Expression of Kynurenine Pathway Metabolic Enzymes in Human Glioma Tissue" (2015). Honors College Theses. 20.