Year: 2020
Type: dissertation
Abstract: Although a major mechanism by which cancer cells evade the immune system is known to be inhibition of direct cytotoxic T lymphocyte (CTL) killing, the genetics underlying this phenotype are poorly understood. To further understand this genetic circuitry, we performed CRISPR-Cas9 screens utilizing CTL-cytotoxicity as a selective pressure across six syngeneic murine cancer models. This led to the identification of 182 core genes that render cancer cells more sensitive or resistant to CTL killing. Follow-up studies comprising correlative analyses’ with TCGA-PanCancer data, secondary verification screens targeting the core set, and in vitro functional assays following knockout of specific core genes, defined the importance of this core set. Specifically, Jmjd6 a jumonji domain-containing bifunctional arginine demethylase and lysl-hydroxylase emerged as a core sensitizer class gene. My observations suggest that Jmjd6 may protect cancer cells from cytokine-mediated toxicity. Additional studies will help to elucidate the precise role of Jmjd6 in cancer intrinsic CTL evasion.
Source: TSpace (University of Toronto)
Author: Rummy Akthar
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funder: HORIZON EUROPE Excellent Science
OpenAlex ID: W3200592513