Faculty, Staff and Student Publications
Publication Date
1-28-2025
Journal
Cell Reports
Abstract
CD226 plays a vital role in natural killer (NK) cell cytotoxicity, interacting with its ligands CD112 and CD155 to initiate immune synapse formation, primarily through leukocyte function-associated-1 (LFA-1). Our study examined the role of CD226 in NK cell surveillance of acute myeloid leukemia (AML). NK cells in patients with AML had lower expression of CD226. CRISPR-Cas9 deletion of CD226 led to reduced LFA-1 recruitment, poor synapse formation, and decreased NK cell anti-leukemic activity. Engineering NK cells to express a chimeric antigen receptor targeting the AML antigen CD38 (CAR38) could overcome the need for CD226 to establish strong immune synapses. LFA-1 blockade reduced CAR38 NK cell activity, and this depended on the CD38 expression levels of AML cells. This suggests parallel but potentially cooperative roles for LFA-1 and CAR38 in synapse formation. Our findings suggest that CAR38 NK cells could be an effective therapeutic strategy to overcome CD226-mediated immune evasion in AML.
Keywords
Humans, Killer Cells, Natural, Leukemia, Myeloid, Acute, Antigens, Differentiation, T-Lymphocyte, Lymphocyte Function-Associated Antigen-1, ADP-ribosyl Cyclase 1, Receptors, Chimeric Antigen, Cell Line, Tumor, Immune Evasion, Immunological Synapses, Female, Animals, Male
DOI
10.1016/j.celrep.2024.115122
PMID
39754720
PMCID
PMC11838179
PubMedCentral® Posted Date
2-19-2025
PubMedCentral® Full Text Version
Author MSS
Graphical Abstract
Published Open-Access
yes
Included in
Bioinformatics Commons, Biomedical Informatics Commons, Genetic Phenomena Commons, Medical Genetics Commons, Oncology Commons