(20h) Breaking through the physical armor of cancer cells

Cancer cells deploy multiple strategies to circumvent or suppress immune-mediated targeting and killing. Identification of biochemical weaknesses in these defenses have led to new immunotherapies that can provide durable clinical responses for a subset of cancers. While cancer cells also may employ physical mechanisms for immune evasion, what these physical defenses are and how to exploit their vulnerabilities remain largely unresolved. In this talk, I will discuss how cancer cells can physically protect themselves from immune attack through modulation of the glycocalyx, the protein- and sugar-rich coating that encases eukaryotic cells. We find that cancer cells can construct a formidable glycocalyx “armor” that shields them from immune cell recognition and killing. We accurately measure the nanoscale thickness of the cellular glycocalyx using an imaging technique called Scanning Angle Interference Microscopy (SAIM). Combining SAIM with powerful genetic strategies to engineer the glycocalyx structure, we show that immune cell-mediated cytotoxicity exhibits a near perfect inverse correlation with the glycocalyx thickness of target cancer cells. Common cancer cell types construct a glycocalyx that is thick enough to provide substantial protection against immune cells, as well as engineered immune cell therapies. In the final part of my talk, I will discuss potential vulnerabilities in the glycocalyx armor and how to capitalize on them in immuno-oncology through cellular engineering strategies and pharmacological interventions.