MM is a genetically complex malignancy of plasma cells that accounts for ~10% of hematologic cancers and remains incurable. The long-term clinical success of the anti-MM therapies is hampered by the presence of an immunosuppressive bone marrow (BM) milieu and exhausted or dysfunctional T lymphocytes. Thus, reactivating endogenous T cell competence appears particularly promising to restore anti-MM immunity and improve the efficacy of current immune therapies. Recent data from Dr. Anderson lab are showing that MM patients who survive longer have an upregulated phagocytosis pathway, a key step needed for an efficient antigen presentation and adaptive anti-MM immune response. The phagocytosis by antigen presenting cells represents a key step in training and rejuvenating T cells to induce an anti-tumor response, and is tightly regulated by the interplay between pro- and anti-phagocytosis checkpoints. The current hypothesis of the lab is that targeting the inhibitory phagocytosis checkpoints will not only improve the efficacy of the anti-MM therapy but also enhance T cell anti-tumor activity, thus improving the outcome of MM patients.

My research project focuses on functionally characterizing a specific inhibitory phagocytosis checkpoint in MM. To achieve this, I will enhance my proficiency in cell culture techniques and acquire the skills to generate dendritic cells (DCs) from monocytes derived from peripheral blood mononuclear cells. Using flow cytometry, I intend to assess the impact of phagocytic stimuli on the phagocytosis of MM cells by DCs. This involves employing CRISPR/Cas9-engineered MM cell lines with deleted genes related to the phagocytosis pathway. Additionally, I will use flow cytometry to examine the influence of soluble factors from the bone marrow microenvironment on the expression of phagocytosis checkpoints. These analyses aim to elucidate the role of the phagocytosis axis in MM.