Investigating T Cell Exhaustion in Multiple Myeloma
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2023-04-26
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Abstract
Multiple Myeloma (MM) is a currently incurable malignancy of plasma cells. Immunotherapies are widely agreed upon to be the most likely avenue through which a cure could be found, however, to become longer lasting, permanent solutions, immunotherapies must overcome persistent antigenic stimulation and immune exhaustion. To this end, there is no currently agreed upon immune signature that denotes which cells are exhausted, and which are healthy. The aim of this thesis was to define this exhaustion signature, using only surface antigens and flow cytometry, in order to sort these exhausted T cells from peripheral blood mononuclear cells (PBMC). Based upon the logic that patients who respond poorly to immunotherapy will have on average more exhausted T cells than patients who respond well to immunotherapy, this project developed and optimized a flow cytometry panel designed to use 14 different T cell markers to phenotypically characterize T cells isolated from patient bone marrow aspirates (BMA). While this project did not succeed in generating a full exhaustion signature due to issues concerning censorship within the cohort which shrunk the sample size, it does show that a repetition of this experiment could elucidate the exhaustion signature with a larger sample size and slight adjustments to the antibody panel. An exhaustion signature for T cells can be generated, using surface markers that can be used for flow cytometric sorting in the future.
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Barakat, E. (2023). Investigating T cell exhaustion in multiple myeloma (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.