Immunotherapy: Open Access
Open Access
ISSN: 2471-9552
ISSN: 2471-9552
Antoun Al Absi, Celine Hoffman, Bassam Janji, Clement Thomas1 and Salem Chouaib
Luxembourg Institute of Health, Luxembourg
Gustave Roussy Cancer Center, France
Posters & Accepted Abstracts: Immunother Open Acc
Natural killers cells (NKs) are effectors of the innate immune system able to kill cancer and pathogen infected cells without pre stimulation through the directed secretion of lytic granule contents. This process requires the formation of a well defined structure termed the immunological synapse (IS) between immune and cancer cells. Previous studies reported that the formation and activity of the IS largely rely on sequential rearrangement of actin filaments (AFs) of NKs. Our results provide evidence that the actin cytoskeleton of NK resistant tumor cells experiences an extensive remodeling at the IS and this process is associated with tumor cell escape from NK mediated cell lysis. Live cell imaging analyses revealed that AFs accumulate in resistant breast tumor cells in a region close to the IS within a few seconds after contact with NKs. The disruption of AFs with Latrunculin B or Cytochalasin D increased conjugate formation and enhanced tumor cell susceptibility to NK mediated cell death. The analysis of a range of epithelial and mesenchymal breast cancer cell lines revealed a striking correlation between the cell mesenchymal status and the ability to remodel the actin cytoskeleton upon NK attack. Also, mesenchymal cells exhibited significantly higher level of resistance to NK mediated cell lysis as compared to epithelial cells. Together our data suggest that actin remodeling is a novel strategy used by breast tumor cells to escape from NK mediated cell death. The precise functions of the prominent and fast accumulation of AFs observed in tumor cells as well as the underlying molecular mechanism are under investigation.
Email: antoun.alabsi@lih.lu