2023 World Conference on Lung Cancer (Posters)-EP02.03. ADAR1 Knockout Results in Loss of Tumorigenicity in a Syngeneic Murine Model of Non-small Cell Lung Cancer.

EP02.03. ADAR1 Knockout Results in Loss of Tumorigenicity in a Syngeneic Murine Model of Non-small Cell Lung Cancer. - PDF(Slides)

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A study conducted by researchers at the Masonic Cancer Center, University of Minnesota, investigated the role of adenosine deaminase for double-stranded RNA 1 (ADAR1) in the development and growth of non-small cell lung cancer (NSCLC). ADAR1 is believed to be a protein that promotes cancer growth and inhibits immune therapy response. The researchers found that the knockout of ADAR1 through CRISPR/Cas9 gene editing had little impact on cell growth or signaling pathways in vitro. However, when ADAR1 knockout cells were injected into immune competent mice, only 1 out of 5 mice developed tumors, while all 5 mice injected with ADAR1 wild-type cells formed tumors. In contrast, when the same experiment was conducted in athymic mice (lacking T cells), all ADAR1 knockout cells formed tumors, albeit at a slower rate than the wild-type cells. These findings suggest that the loss of tumorigenicity observed in ADAR1 knockout NSCLC cells is partially dependent on the presence of T cells.<br /><br />The researchers also investigated the impact of ADAR1 knockout on type I interferon (IFN) signaling, a pathway implicated in response to immune checkpoint therapies. They found that ADAR1 knockout had little effect on type I IFN signaling through STAT1 and PKR, two key proteins in the pathway. These findings suggest that ADAR1 knockout does not influence the response to immune therapies targeting this pathway.<br /><br />Overall, this study demonstrates that the knockout of ADAR1 reduces the tumorigenicity of NSCLC without substantially impacting cell growth in vitro. The loss of tumorigenicity is at least partially dependent on the presence of T cells. Further research is needed to better understand the critical pathways mediated by ADAR1 in NSCLC.

Asset Subtitle

Manish Patel

Meta Tag

Speaker Manish Patel

Topic Tumor Biology: Preclinical Biology - Regulatory Mechanisms

Keywords

ADAR1

NSCLC

cancer growth

immune therapy response

CRISPR/Cas9

tumors

T cells

interferon signaling

immune checkpoint therapies

cell growth