The interplay between innate immune cells and antibodies to control cancerous growth is of central importance for mediating direct anti-tumor effects and the induction of long-lived anti-tumor immunity. Phagocytosis of antibody-opsonized cells by macrophages through Fc gamma receptor interactions is well characterized and leads to cell death through target cell engulfment into phagosomes. By contrast, the contribution of the related process called trogocytosis, involving the ingestion of limited amounts of the target cell by phagocytic cells, to cell attrition is less certain. In the current study we have developed a high throughput, quantitative assay to distinguish whole cell phagocytosis and trogocytosis for different macrophage:breast cancer cell combinations. These analyses, combined with long term microscopic imaging, demonstrate that trogocytosis leads to death of HER2-overexpressing breast tumor cells. The implementation of multifocal plane microscopy to investigate trogocytic events at high spatiotemporal resolution reveals that these processes involve tubular extensions of opsonized tumor cells that are subsequently pinched off by the recipient macrophage. Of relevance to the design of second generation antibodies with improved efficacy, antibody engineering to enhance Fc gamma receptor interactions results in increased trogocytic activity. Collectively, these studies have significance to the rapidly expanding use of antibodies to treat cancer.
This research was supported in part by grants from the Cancer Prevention and Research Institute of Texas (CPRIT, RP 110069) and the National Institutes of Health (R01 GM85575).
Citation Format: Ramraj Velmurugan, Dilip Challa, Sripad Ram, Raimund Ober, E. Sally Ward. Macrophage-mediated trogocytosis leads to death of antibody-opsonized tumor cells. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr B089.