Dissecting Complex Heterogeneity of Immune Cell and Immuno-Oncology Interactions at the Single Cell Level Using Droplet Microfluidics

Presenter: Seamus McKenney

Research Category: Physical and LIfe Sciences
Student Type: Graduate
Additional Authors: Saheli Sarkar
PI: Tali (Tania) Konry
Award Winner Category: Physical and Life Sciences

Immune cells are intrinsically heterogeneous in their phenotypic functionality by nature. Understanding that heterogeneity is critically important in learning how the immune system works in fighting cancer and other diseases. However, the majority of immune cell assays used in research fail to capture this heterogeneity, relying instead on averaging responses from many cells in bulk culture. Microfluidics has become increasingly popular for dissecting heterogeneous immune cell interactions. Our novel high-throughput droplet microfluidic technology has dissected these interactions at the single cell level on a dynamic time scale. We have monitored several immune cell types interacting with a variety of cell pairs to understand the underlying heterogeneity that exists in these interactions. Natural killer (NK) cells, cells of the innate immune system responsible for identifying and killing infected cells and cancerous cells, have been encapsulated in droplets with multiple myeloma (MM) cells to monitor NK cell cytotoxicity. By adding an immunomodulatory drug, we observed increased cytotoxic ability while still observing a heterogeneity of responses among single cells. In the same platform, we utilized a therapeutic NK cell line against the same MM cells, and again saw an increase in MM cell death compared to primary NK cells. We have also examined the interaction of T-cells and dendritic cells (DC) in droplets. DC-mediated activation was monitored in real-time, developing calcium signaling profiles of individual cells using a fluorescent calcium-sensitive dye. Our platform represents a robust, dynamic technology capable of elucidating the inherent heterogeneity that is characteristic of immune cells and immuno-oncology interactions.