Researcher creates ‘Instagram’ of immune system, blending science, technology
Being on the cutting edge of science and technology excites Hollings Cancer Center (HCC) researcher Carsten Krieg, Ph.D. Each day, he walks into his lab that houses a mass cytometry machine aptly labelled Helios. Krieg explains how it can heat plasma up to 6,000 degrees Celsius, levels comparable to temperatures found on the sun.
This allows the German native, who recently joined the faculty of the Medical University of South Carolina’s departments of immunology and dermatology, to accomplish an interesting feat. He creates a sort of ‘Instagram’ of a person’s immune system. For cancer patients on experimental immunotherapy treatments, the practical application is obvious and exciting, he said.
“What I use here is a very new and nerdy technology, which is called mass cytometry, that allows you with a very high sensitivity to make pictures of your immune system. And this is possible because there's artificial intelligence, machine learning combined with algorithms that can make a very complex system easy to visualize.”
Basically, how it works is that researchers stain cells using rare metal-conjugated antibodies that target surface and intracellular proteins. “Normally in biological tissues, there are no rare metals, so this technique offers greater sensitivity in detecting targets.”
Inside the Helios, the cells are ionized using an inductively-coupled plasma. The ions derived from each stained cell are maintained in discrete clouds that can be detected in a mass spectrometer. The technique can potentially detect up to 100 markers per cell, although, due to practical restrictions, about 40 are more realistic, he said. Then researchers use artificial intelligence and bioinformatics to create a two-dimensional mapping that can read the results, creating an Instagram of millions of blood cells.
This is critical as Krieg and other cancer researchers hope to advance the field of immunotherapy. Though immunotherapy has shown great promise, the vast majority of patients either don’t respond, have adverse side effects or relapse. Krieg, who comes to HCC from the University Research Priority Program (URPP) in Zurich, Switzerland, wanted to know if the technology could be used to predict which patients might respond to certain treatments.
While in Zurich, he and his colleagues decided to use the technique to study melanoma. The research identified biomarkers in the blood that can predict whether metastatic melanoma cancer patients will respond positively to immunotherapy. The goal was to see if a blood test for these biomarkers could identity those who are likelier to benefit, while allowing “non-responders” to begin other treatments without losing time, he said. “It’s a decision instrument for physicians and for the health care system.”
It’s also a powerful research tool as it gets to the mechanisms behind what makes immunotherapy work. The recent study found an immune cell type known as classical monocytes in the peripheral blood may be a potential biomarker for patients who will respond to anti-PD-1 immune checkpoint therapy in metastatic melanoma. “Surprisingly, what we clearly found is that it’s the frequency of monocytes that is enhanced in responders over non-responders before immunotherapy.”
Hollings Cancer Center