Rochelle Ellison
Program: Immunology
Current advisor: Kodi S. Ravichandran, PhD
Undergraduate university: University of California-Los Angeles
Research summary
Phagocytic clearance of apoptotic cells, a process known as efferocytosis, is essential for tissue homeostasis. By triggering the production of anti-inflammatory cytokines and pro-resolving mediators, effective efferocytosis dampens inflammation and promotes tissue repair. While this response is beneficial in most situations, solid tumors may take advantage of efferocytosis to induce an immunosuppressive microenvironment. Not only is cell death prominent in solid tumors, but live tumor cells may also expose phosphatidylserine (PS), a signal typically indicative of cell death and one which serves as a ligand for many efferocytic receptors. Tumor-associated macrophages (TAMs) are the predominant professional phagocytes in the tumor microenvironment. As a result of their functional heterogeneity, TAMs have been associated with both tumor regression and tumor progression. To determine the role that efferocytosis plays in the immunosuppressive polarization of TAMs, we engineered chimeric receptors for efferocytosis (CHEFs) that modulate TAM responses to PS+ tumor cells. We first fused the PS recognition domain of the efferocytic receptor, TIM4, to the signaling domain of a cytoplasmic efferocytosis adaptor protein, ELMO1. This CHEF, dubbed TELMO, boosted efferocytosis and anti-inflammatory cytokine production in macrophages. For our second CHEF, we combined the PS recognition domain of TIM4 with the pro-inflammatory Toll/IL-1 receptor (TIR) domain of TLR4 thereby allowing for robust immune activation in response to PS signaling. Ultimately, examining tumor responses to TAMs expressing these CHEFs may elucidate the immunomodulatory dynamics of TAM and tumor cell interactions, paving the way for innovative anti-tumor therapeutics.
Graduate publications