Identification of drivers of monocyte-mediated trogocytosis of tumor cells.

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B113
Abstract ID: 5698

Presenting Author:
Cristina F Contreras , Graduate Student at NCI, NIH, Univ. of Oxford Med. Sci. Div.

Abstract:

Monocytes are innate immune cells recognized for their plasticity in response to cancer. Tumor-associated monocytes and other myeloid cells can take on tumor-promoting functions and have been linked to worse clinical outcomes including poor response to immunotherapy in patients with solid tumors. Our group has found trogocytosis, a poorly understood form of cell interaction, to be a mode of monocyte-tumor cell communication that impacts myeloid cell activation. The key regulators governing monocyte-mediated tumor cell trogocytosis and its effects on the balance of immune suppression vs activation are yet to be characterized. In this study, we present a genome-wide CRISPR/Cas9 screen to identify the drivers of tumor-cell trogocytosis by monocytes. Monocyte-mediated trogocytosis of tumor cells was tested by co-culture of human GeCKOv2-transduced monocytic THP-1 cells with a fluorescently labelled human osteosarcoma cell line. Functional populations were sorted by FACS, and genomic analysis was performed to assess KO enrichment. While REACTOME analysis showed enrichment of some processes involved in phagocytosis, our findings reveal hits distinct from those in phagocytosis-based screens, which was confirmed by live cell microscopy. Select genes were chosen for validation and functional exploration in primary human monocytes. This integrative genomic study provides insights into our understanding of monocyte-function in cancer and informs the design of myeloid-mediated therapies.