Prostate Cancer Lab #17: Single cell and cancer heterogeneity analysis (Wendy Fantl)

“We’ve had DNA and RNA seq. Those are all great proxies for proteins. I don’t want to monkey around anymore. I want to get a good definition of what’s happening.” –Brian McCloskey

“You need somebody that’s really, really committed to understanding how new technologies can work. You need really good physician scientists.” –Wendy Fantl 

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Wendy Fantl, PhD, Assistant Professor, Urology, Stanford Medicine, led a discussion on “Single cell and cancer heterogeneity analysis”. She gave a basic introduction to two single cell technologies she works with: “Cytometry by time of flight” (“CyTOF”) and “CODEX” (Co-detection by indexing) multiplex imaging. They provide important information at a single cell level about protein expression, using antibodies to identify cells based on the types of antigens or markers on the surface of the cells.

Why are these single cell technologies important?

Tumors are a mass of heterogeneous cell types. Single cell proteomic technologies allow you to unravel tumor heterogeneity, to peer inside and identify key cell types in the tumor, their numbers, and how they are arranged spatially into neighborhoods. They can help characterize immune function and cancers, and understand cells’ response to therapy. You can identify minority cell populations that are the bad guys, that have key roles in tumor initiation, maintenance, cell migration, and drug resistance.

For example, Wendy shared research that looked at blood collected from men with metastatic prostate cancer and found natural killer cells that didn’t kill anymore. With CyTOF, you could measure populations of these distinctive natural killer cells to monitor disease progression.

Since CyTOF looks at cells in suspension (usually blood), you lose information about which cell is next to which cell. That’s important, and that brings up seeing cellular neighborhoods using CODEX multiplex imaging. For example, you can see one neighborhood that has tumor cells, or another that has immune cells. A ”hot tumor”, which is more likely to respond to immunotherapies, has immune cell infiltration into the tumor cells in a neighborhood, while a “cold tumor” does not.

Brian McCloskey asked how he could have a conversation with his doctor about using these technologies in his treatment decision-making process. “We’ve had DNA and RNA seq. Those are all great proxies for proteins. I don’t want to monkey around anymore. I want to get a good definition of what’s happening.”

Wendy responded: “You need somebody that’s really, really committed to understanding how new technologies can work. You need really good physician scientists. They need to really get it. Sadly, a lot of physicians don’t have time. I am a former patient. I had ovarian cancer. I fired so many doctors you don’t even want to know. I told them: ‘I am the patient from hell. I am going to ask you questions, I am the boss of me. I am a scientist and a cancer biologist, and I am not a dummy.’ I did find somebody who was amazing. She’s one of my best friends, and we are collaborating. You need somebody who’s really going to engage and get what it is, and a lot of them they just don’t want to.”