Immune Dysfunction in Myeloma: Characterisation and Generation of IL-17-secreting Lymphocytes and Immune Manipulation using Oncolytic Virotherapy

Recent years have seen several notable advances in therapy for multiple myeloma (MM), which have translated into impressive improvements in progression-free and overall survival rates. Nevertheless, patients afflicted with this relatively common, incurable cancer can typically expect ever shortening treatment-free intervals between sequential therapies; relapsed, treatment-refractory disease remains common. Myriad experimental and observational studies comprehensively document a state of profound immune dysfunction in MM. Intriguingly, an accruing body of evidence indicates that immune dysregulation is not only progressive and correlated with disease stage, but that it may actually contribute to the pathogenesis of the disease. This thesis will examine the contribution of the recently described Th17 subset of T cells to immune dysfunction in MM and the mechanisms of their generation before assessing the use of a novel oncolytic virotherapy as an immunomodulatory therapy for MM.