Natural phenomena (trogocytosis and cell fusion) between ovarian cancer and immune system cells

Abstract

Understanding the complex behavior of immune system cells, such as B lymphocytes and T lymphocytes, in responding to cancerous growth is of central importance to cancer treatment. Natural phenomena, specifically trogocytosis and cell fusion, can lead to the development of metastases by acquiring characteristics such as genetic and epigenetic heterogeneity, chemotherapeutic resistance and immunological tolerance. Trogocytosis is a rapid absorption of membranes and associated molecules from one cell by another, while cell fusion is an incorporation of membranes, undergoing rapid nuclear reprogramming and epigenetic modifications to form hybrid cells with new genetic and phenotypic properties. Objective: To evaluate whether the monoclonal antibody (Oregovomab) used to treat ovarian cancer can induce antigenic modulation, promoting trogocytosis and cell fusion in vitro and in vivo after binding to their respective target cells. In addition, we will evaluate the kinetics of specific cell populations, such as circulating tumor cells, B and T cells, that may be susceptible to factors that stimulate these phenomena, and evaluate if exogenous factors, such as neuropeptides, can affect trogocytosis. Methodology: To explore the role of trogocytosis and cell fusion in oncogenesis and therapeutic response, we will use both in vivo and in vitro assays. For in vivo analysis, we will use BALB/c-H2dm2/KhEgJ mice (these mice are available in the Birbrair's lab), which carry the spontaneous H2dm2 mutation, a major histocompatibility variant, and NSG branded mice lack mature T, B and natural killer cells. For in vitro evaluation we will perform cell culture, immunofluorescence, flow cytometer and single cell RNAseq (collaboration with the UWBC (University of Wisconsin - Biotechnology Center). Expected results: Cells that undergo trogocytosis and cell fusion can be a key component in cancer metastasis, and thus, evolve as a therapeutic target. Furthermore, our findings may have important implications regarding the use of mAbs in cancer immunotherapy. (AU)