Agonism of TLR9 and TLR7 to enhance NK cell-mediated clearance of B-cell lymphoma
Author ORCID Identifier
0000-0002-6889-8318
Advisor Information
Dr. Paul W. Denton
Location
MBSC Ballroom - Poster #310 - G
Presentation Type
Poster
Start Date
4-3-2022 2:00 PM
End Date
4-3-2022 3:15 PM
Abstract
The innate immune system is the front line of the body’s defenses. Innate effector cells, including natural killer cells (NK) cells, represent some of the first immune cells to respond to malignancies or infections. One of two primary mechanisms for NK cell target recognition is antibody-dependent cellular cytotoxicity (ADCC). This mechanism relies on antigen specificity. The clinical efficacy of anti-CD20 (aCD20) antibodies (e.g., Rituximab™) showcase the impact of NK-cell-mediated ADCC on B-cell lymphomas. NK cells are typically activated for performing effector functions by exposure to key cytokines, although these cytokines are not necessarily produced by the NK cells themselves. This represents indirect activation via crosstalk between multiple cell types. Cells that produce these cytokines include monocyte/macrophages and plasmacytoid dendritic cells (pDCs). This activation cascade, for example, occurs following toll-like receptor 9 (TLR9) and toll like receptor 7 (TLR7) agonism in pDCs which in turn produce interferon alpha (IFN-a) that subsequently induces interferon-g production and NK cell activation. This series of signals leads to physiologically relevant levels of cytokines for activating NK cells to perform their effector function: this is precisely the natural route of immune activation that I propose to explore in my study.
Scheduling Link
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Agonism of TLR9 and TLR7 to enhance NK cell-mediated clearance of B-cell lymphoma
MBSC Ballroom - Poster #310 - G
The innate immune system is the front line of the body’s defenses. Innate effector cells, including natural killer cells (NK) cells, represent some of the first immune cells to respond to malignancies or infections. One of two primary mechanisms for NK cell target recognition is antibody-dependent cellular cytotoxicity (ADCC). This mechanism relies on antigen specificity. The clinical efficacy of anti-CD20 (aCD20) antibodies (e.g., Rituximab™) showcase the impact of NK-cell-mediated ADCC on B-cell lymphomas. NK cells are typically activated for performing effector functions by exposure to key cytokines, although these cytokines are not necessarily produced by the NK cells themselves. This represents indirect activation via crosstalk between multiple cell types. Cells that produce these cytokines include monocyte/macrophages and plasmacytoid dendritic cells (pDCs). This activation cascade, for example, occurs following toll-like receptor 9 (TLR9) and toll like receptor 7 (TLR7) agonism in pDCs which in turn produce interferon alpha (IFN-a) that subsequently induces interferon-g production and NK cell activation. This series of signals leads to physiologically relevant levels of cytokines for activating NK cells to perform their effector function: this is precisely the natural route of immune activation that I propose to explore in my study.