New nondestructive imaging technique tracks immune cell health

When a patient is facing certain cancers or an immune condition, clinicians turn to their white blood cells for clues about the progression of both diseases and their treatments. From a standard blood draw, a clinical lab isolates peripheral blood mononuclear cells (PBMCs), which are predominantly immune cells, and then counts the abundance of different cell types, along with some basic measures of how they're functioning.

"PBMCs can be isolated clinically really easily, and they're already used in the clinical workflow," says Melissa Skala, an investigator in biomedical engineering at the Morgridge Institute and senior author of a new study in Biophotonics Discovery. "So, the question is, what can we get from them that we aren't already getting?"

Skala and her Morgridge Institute lab, including PhD student Jeremiah Riendeau, are working on bringing advanced imaging techniques to bear on the quest to retrieve as much information as possible from immune cells. In the process, they hope to help improve diagnosis and treatment of immune system-related conditions like blood cancers, lupus, sepsis, and cognitive decline. Additionally, PBMCs are the starting material for CAR T cell therapies, which engineer a patient's own immune cells to fight certain cancers. Understanding immune dynamics in these engineered cells in more nuanced and comprehensive ways than are currently available to clinicians could improve the outcomes of patients undergoing treatments including CAR T cell therapy.

The ability to learn more about immune cells and their function without destroying them means the technique could be used in applications like assessing the fitness of immune cells before they're administered as a treatment.

"You can continue using the samples after this analysis," says Riendeau. With other techniques, "if you want to study metabolism you have to add different reagents to the sample, and that can be harmful to the cells."

Skala adds that "a lot of starting material for cell therapies are PBMCs. If you could do something to assess the fitness of those cells before processing them for cell therapy, that would be nice."

Going forward, the team hopes to work with collaborators in hospitals to develop clinical applications for this analysis and bring better diagnosis and treatment outcomes to cancer and immune disorder patients.

What are PBMCs?

"The innate immune cells," says Riendeau, "are kind of like the first responders, and then later on the adaptive immune cells will come in and help out with a more target-specific approach."

Why is immune metabolism so important?

The researchers found in the new study that innate immune cells are the most metabolically distinct, which likely is due to their ability to be highly reactive to threats and quickly ramp up their activity. Meanwhile, adaptive immune cells activate more slowly and need to be able to sustain energy over longer periods. But, elevated metabolic activity isn't always good, and in conditions related to chronic inflammation, markers of activation can be an indicator that something is wrong.

"Generally, you don't want to have constant, ongoing immune reactions. So, immune cells in the bloodstream are kept locked down in a quiescent state. But when there is some infection or other problem, like cancer, this would cause an immune reaction and activate metabolic pathways," says Riendeau. "Having an understanding of the relative amounts of white blood cells is already used as a diagnostic biomarker. Adding this metabolic piece can tell you additional facts about the activation state of the immune cells."

What can advanced imaging tools reveal about cell dynamics? 

Riendeau says their new type of analysis using OMI can make sense of heterogenous metabolic states between cell types. For example, a subset of immune cells might be hyperactive while others remain quiescent. A bulk measurement averaging across the whole sample would hide those differences and obscure how the immune system is responding to an infection or whether cell therapy is successfully treating a cancer. But, with the ability to nondestructively measure metabolism of single immune cells in a complex sample, researchers will be able to push forward how we understand our body's defense systems.

Source:

Morgridge Institute for Research

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