GCI Spotlight - Chu-Han Feng

Presenter: Chu-Han Feng

When: Friday November 25th, 4pm

Where: GCI 5th floor atrium

Dual inhibition of PTPN1 and PTPN2 to enhance human natural killer cell anti-tumor cytolysis functions: Natural killer (NK) cells are innate lymphocytes with spontaneous cytolysis functions to eliminate virus-infected cells and tumor cells that are recognized as non-self and altered-self-threats. NK cells have been recognized as ‘off-the-shelf’ immune cell sources for allogenic anti-tumor immunotherapy with lower risks to develop severe side effects such as cytokine storm and graft-versus-host diseases based on clinical observations. Our current knowledge of receptor signaling in regulating NK cytolytic function remains limited. Here, we reported PTPN1 and PTPN2 as novel targets that can be pharmacologically inhibited together to sensitize human NK cells to cytokine activation in a reversible manner. Sensitized NK cells increased production of pre-formed cytolytic granules perforin and granzyme B at a steady state and pro-inflammatory cytokines IFN-γ upon cell activation, resulting in enhanced tumor cell cytolysis in vitro. Furthermore, NK cells upregulated the expression of early activation marker CD69. Mechanistically, dual inhibition of PTPN1 and PTPN2 sensitized NK cells to IL-2 stimulation with upregulation of phosphorylated STAT members. Our research observations indicate that PTPN1 and PTPN2 are novel targets to improve the potency of current NK cell-based anti-tumor immunotherapy.