Event Title

Inhibition of IL-1β Secretion in Tumor Associated Macrophages using Bruton’s Tyrosine Kinase Inhibitors, Ibrutinib and Acalabrutinib

Presenter Information

Kallie Jiang, Oberlin College

Location

Science Center, Bent Corridor

Start Date

10-27-2017 6:40 PM

End Date

10-27-2017 7:20 PM

Research Program

The Ohio State University Summer Undergraduate Course Creating Excellence in Scientific Study (SUCCESS) Program

Poster Number

32

Abstract

IL-1β is a cytokine that is associated with the expansion of myeloid derived suppressor cells (MDSCs). In cancer patients, MDSCs are particularly problematic as they suppress anti-tumor T-cell and NK cell functions. IL-1β expression could possibly be mediated by treating tumor associated macrophages (TAMs), immune cells that have been polarized to a “pro-tumor” phenotype, with the drug Ibrutinib, a Bruton’s Tyrosine Kinase inhibitor (BTK). Ibrutinib can bind to BTK on (TAMs) and possibly inhibit the function of the NLRP3nflammasome which is hypothesized to be conjugated to BTK on TAMs. Inhibition of this inflammasome may decrease the amount of IL-1β expressed in TAMs. As a result, Ibrutinib, which is mainly used to treat patients with B-Cell malignancies, could be beneficial in the treatment of a wider range of patients with diseases that could range from triple negative breast cancer to melanoma. Currently, there is no universally accepted method of generating and characterizing TAMs. Therefore, in addition to researching IL-1β expression in TAMs, the Carson lab also seeks to develop an effective and comprehensive method of generating TAMs in vitro.

Major

Biochemistry

Project Mentor(s)

Brooke Brenner and William Carson, Comprehensive Cancer Center, The Ohio State

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Oct 27th, 6:40 PM Oct 27th, 7:20 PM

Inhibition of IL-1β Secretion in Tumor Associated Macrophages using Bruton’s Tyrosine Kinase Inhibitors, Ibrutinib and Acalabrutinib

Science Center, Bent Corridor

IL-1β is a cytokine that is associated with the expansion of myeloid derived suppressor cells (MDSCs). In cancer patients, MDSCs are particularly problematic as they suppress anti-tumor T-cell and NK cell functions. IL-1β expression could possibly be mediated by treating tumor associated macrophages (TAMs), immune cells that have been polarized to a “pro-tumor” phenotype, with the drug Ibrutinib, a Bruton’s Tyrosine Kinase inhibitor (BTK). Ibrutinib can bind to BTK on (TAMs) and possibly inhibit the function of the NLRP3nflammasome which is hypothesized to be conjugated to BTK on TAMs. Inhibition of this inflammasome may decrease the amount of IL-1β expressed in TAMs. As a result, Ibrutinib, which is mainly used to treat patients with B-Cell malignancies, could be beneficial in the treatment of a wider range of patients with diseases that could range from triple negative breast cancer to melanoma. Currently, there is no universally accepted method of generating and characterizing TAMs. Therefore, in addition to researching IL-1β expression in TAMs, the Carson lab also seeks to develop an effective and comprehensive method of generating TAMs in vitro.