Researchers of Fluidigm: Noel de Miranda’s Immunogenomics Group

Our ‘Researchers of…’ articles explore behind the scenes in the labs of researchers who work with the EACR’s Industry Partners. This article is about the de Miranda lab’s use of Imaging Mass Cytometry in immunotherapy research.

There are possibilities and limitations to any cancer treatment, where the expectation of a favorable outcome might only hold true for a subset of patients. This is the case for most immunotherapies.
Consider a cancer patient, waiting to hear from their oncologist with high hopes they are a candidate for a new immunotherapy treatment. The promise of immunotherapies like checkpoint blockade inhibitors is tangible as the revolutionary approach provides a growing number of options for a variety of cancer types. Yet currently, only under 15% of cancer patients actually benefit.
Noel de Miranda
Dr. Noel de Miranda

Immunotherapies are focused on stimulating a patient’s own immune system to recognize and destroy cancer cells. Dr. Noel de Miranda, PhD, leads the Immunogenomics group as a Principal Investigator at Leiden University Medical Center. The group combines immunology and genetics to both develop innovative immunotherapies and broaden efficacy of existing ones.

A renewed interest in cancer immunology

One of De Miranda’s ongoing projects focuses on identification of and interactions between immune cells and tumor cells within the cancer microenvironment. A renewed interest in cancer immunology over the last decade, based on successes with immunotherapy and the advent of new technologies aimed at more in-depth investigation, have paved the way for looking deeper into tumors and at multiple features simultaneously.

Given that composition of immune cell compartments in a tumor is known to be a major determinant of clinical presentation, De Miranda aims to better understand the types of cells within a tumor along with the myriad of mechanisms that play a role in response to immunotherapy. To address this, he takes advantage of some major breakthroughs in both single cell profiling and multiplex imaging technologies.

One of the coolest things with this technology in my opinion is our ability to distinguish… different flavors of macrophages, monocytes, dendritic cells…

How they’re using Imaging Mass Cytometry

Using Imaging Mass Cytometry™, De Miranda and his group investigate cell phenotypes, cell location within a tissue and even context among cell subsets, enabled through the parallel detection of several markers simultaneously with the precision of heavy metal-labeled antibodies. In order to capture the comprehensive complexity of a tumor, the group built a highly multiplexed panel of 40 markers, including immune cell lineage markers, differentiation and activation markers, immunomodulatory molecules and therapeutic targets, cell signaling molecules and tissue type-specific markers to map the different components of the tissue and reveal how the accumulation of immune cells associates to features of tumor cells.

“One of the coolest things with this technology in my opinion is our ability to distinguish tumor-associated cell subsets, namely different flavors of macrophages, monocytes, dendritic cells – which I think is quite challenging to do with other technologies,” Dr. Miranda says. “We can also see the full complexity of the microenvironments in the images, something not typically captured with previous approaches.”

“An unanticipated combination of markers”

In the search for new immunotherapy targets, he notes that IMC allows the exciting discovery of things they didn’t know existed or are not able to explain based on current knowledge. For example, the group has seen novel associations through an unanticipated combination of markers. They have also been able to investigate in depth the relation between all subsets that have been identified and whether differences in the spatial arrangements of these subsets also play a role in pathogenesis. “And we do this all in context of enhancing checkpoint blockade treatments for cancer patients that are undergoing immunotherapy.”

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