Presentation Title

Agonism of TLR9 and TLR7 to enhance NK cell-mediated clearance of B-cell lymphoma

Presenter Information

Anna MahrFollow

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.

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Mar 4th, 2:00 PM Mar 4th, 3:15 PM

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.