Abstract 199: Increased killing potential of ex vivo differentiated human natural killer cells in the presence of HOXB4

Abstract

Abstract We have previously shown that human umbilical cord blood CD34+ progenitor cells undergo in vitro differentiation into functional NK cells and that their co-culture in the presence of HOXB4 transduced stromal MS5 cells resulted in an increase in differentiated NK number. The present study was conducted to compare the stromal effect on NK lytic potential in the presence and absence of HOXB4. Our results provide evidence that HOXB4 transduced MS5 cells as compared to transduced, GFP (+) MS5 cells induced highly differentiated cytotoxic NK cells. Importantly, this difference was not due to the expression of activating NK receptors but was associated with an increased induction of granzyme B transcription and degranulation in response to stimulation with NK cell susceptible targets. DNA microarray-based global transcriptional profiling confirmed the up-regulation of Granzyme B. We provide evidence that HOXB4 is a crucial regulator of NK lytic function and that its use in generating functional NK cells with increased lytic potential may be significant for hematologic malignancies. Our findings provide further evidence that HOXB4 is a crucial regulator of NK function and that its use in generating functional NK cells with increased lytic potential may be significant for cancer immunotherapy. Citation Format: Salem Chouaib, Arash Nanbakhsh, Cécile Pochon, Sophie Amsellem, Gianfranco Pittari, Jean-Henri Bourhis. Increased killing potential of ex vivo differentiated human natural killer cells in the presence of HOXB4. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 199. doi:10.1158/1538-7445.AM2014-199