Booth Id:
CELL008
Category:
Cellular and Molecular Biology
Year:
2023
Finalist Names:
George, Anjali (School: University School of Milwaukee)
Abstract:
Natural Killer (NK) cells -both circulating (cNK) and liver resident (lr-NK) - are a major
component of innate host defense against Hepatocellular carcinoma (HCC). NK cell dysfunction
is associated with the development and progression of HCC. Using single cell RNA sequencing
data, we analyzed the gene expression profiles (GEP) of NK cell populations in four patients
with HCC based on their location in the liver. We isolated and compared NK cell transcriptomes
among samples from specific sites in the liver: tumor core, tumor periphery, and adjacent normal
liver. Seven NK cell clusters were identified, reflecting differences in phenotype and maturity.
The GEP of NK cells in tumor core and periphery were similar, but distinct compared to those
from adjacent normal liver. NK cells in tumor core and periphery were predominantly lr-NK
cells and mature cNK cells while the principal constituent in adjacent normal liver was a unique
cluster of NK cells that harbored markers of cytotoxicity and immune exhaustion. Differential
expression of genes regulating key immunomodulatory pathways were noted between lr-NK
cells in tumor core vs. normal liver and tumor periphery vs. normal liver. The functional
significance of differences in GEP noted between NK cells in tumor core and tumor periphery
compared to adjacent normal liver needs further exploration to elucidate the complex immune
milieu of HCC. More importantly, the markers of cytotoxicity and immune exhaustion noted in a
subset of NK cells excluded from the tumor core highlights the therapeutic potential of NK cell
immune modulation in HCC.