eprintid: 31764
rev_number: 14
eprint_status: archive
userid: 6748
dir: disk0/00/03/17/64
datestamp: 2025-02-06 13:51:29
lastmod: 2025-02-11 14:36:16
status_changed: 2025-02-06 13:51:29
type: doctoralThesis
metadata_visibility: show
creators_name: Ton, Nu Hoang Quy Gigi
title: The Role of IKZF3 Expression in T Cells of Patients with Multiple Myeloma
subjects: ddc-570
subjects: ddc-610
divisions: i-910100
adv_faculty: af-05
abstract: In my dissertation, I investigated the role of IKZF protein family in T cells by establishing a CRISPR Cas9 model in CD8+ T cells. I analysed the down-stream signaling pathway of IKZF3 by high-throughput RNA bulk sequencing method and proteomics analysis, including co-immunoprecipitation and protein binding analysis, to identify function and regulatory mechanisms of this protein family in T cells.
I demonstrated that IKZF3 regulates the IFN-inducible gene expression, and thus, IKZF3 KO CD8+ T cells showed increased expression of cell surface markers for T cell activation and exhaustion. In addition, I showed that IKZF3 binds to IKZF1 at the C’ terminal for heterodimerization in exhausted CD8+ T cells. Whereas in the absence of IKZF1, IKZF3 forms heterodimer complexes with MX1 and DTX3L. Single KO of IKZF1 in CD8+ T cells showed that the transcription factor regulates gene expression involved in T cell activation on transcriptomic level and on functional level, I found increased cell surface marker expression of T cell activation. In MM patients, I found that newly diagnosed MM patients with high IKZF3 expression levels have significantly higher amount of effector T cells.
In conclusion, I found evidence of IKZFs playing a superior role in T cell activation and drive T cells to exhaustion, and gave preliminary conclusions of the IKZF protein family functionality in CD8+ T cells. Previously, studies were mainly focusing on IKZF within the B cell compartment as a critical regulator of B cell development and functionality. My findings indicate novel IKZF regulatory mechanisms within the CD8+ T cell compartement, providing new insights in T cell modulation, and therefore, making the transcription factor protein family a promising target for cancer immunotherapy.
date: 2025
id_scheme: DOI
id_number: 10.11588/heidok.00031764
ppn_swb: 1917002483
own_urn: urn:nbn:de:bsz:16-heidok-317646
date_accepted: 2025-01-21
advisor: HASH(0x55e83afcc0c8)
language: eng
bibsort: TONNUHOANGTHEROLEOFI
full_text_status: public
place_of_pub: Heidelberg
citation:   Ton, Nu Hoang Quy Gigi  (2025) The Role of IKZF3 Expression in T Cells of Patients with Multiple Myeloma.  [Dissertation]     
document_url: https://archiv.ub.uni-heidelberg.de/volltextserver/31764/1/Ton_nu_Hoang_Quy_Gigi_03_09_1994_Dissertation.pdf