Kerry S. Campbell, PhD
Fox Chase Cancer Center
Philadelphia, PA 19111
(215) 728-2412 fax
Most Recent Peer-reviewed Publications
- Integrin receptors on tumor cells facilitate NK cell-mediated antibody-dependent cytotoxicity
- Carbohydrate-mediated modulation of NK cell receptor function: Structural and functional influences of heparan sulfate moieties expressed on NK cell surface
- The AP-2 clathrin adaptor mediates endocytosis of an inhibitory killer cell Ig-like receptor in human NK cells
- Combination immune therapies to enhance anti-tumor responses by NK cells
- Genome-wide siRNA screen reveals a new cellular partner of NK cell receptor KIR2DL4: Heparan sulfate directly modulates KIR2DL4-mediated responses
Research and Clinical Interests
Signal Transduction in Natural Killer Cells
Natural Killer (NK) cells constitute 10-15% of peripheral blood lymphocytes, and provide an important sentinel component of innate immune responses by killing certain tumor cells and virally infected cells. Improved understanding of human NK cell-mediated cytotoxicity has recently evolved from the discovery of one of their key controlling elements, Killer Cell Inhibitory Receptors (KIR). KIR bind major histocompatibility complex (MHC) class I molecules on adjacent cells, and MHC class I binding suppresses NK cell killing through the transmission of dominant "negative signaling" through KIR. MHC class I molecules are normally expressed on virtually every cell of the body. The loss of MHC class I by some tumor cells and virally infected cells unleashes their killing due to elimination of the KIR negative signals.
Alternatively, a distinctive member of the KIR family of receptors, named KIR2DL4, is highly conserved in primates, including humans. This is an activating receptor that stimulates NK cells to secrete cytokines, but uniquely does not stimulate cytotoxicity responses. KIR2DL4 is only expressed on a small subset of activated NK cells in certain humans, while some individuals cannot express this receptor at all, due to a common genetic polymorphism. Therefore, NK cell responsiveness may be compromised in the many individuals that cannot express this receptor. Some evidence indicates that KIR2DL4 plays a role in pregnancy, but it may also be important in NK cell responses toward tumors or virus-infected cells.
My laboratory studies the molecular mechanisms by which inhibitory KIR and KIR2DL4 regulate NK cell responses. The main focus of the lab is to dissect the signal transduction crosstalk between these activating and inhibitory receptors to define how they control NK cell responses toward tumors and virus-infected cells.