Going Beyond PDL-1. Q&A with Dr. Nina Radosevic- Robin, MD.

Categorized As:

Dr. Nina Radosevic-Robin, MD, is a Board-Certified Surgical/Molecular Pathologist at Centre Jean Perrin, a Sr. Scientist within the Unit 1240 of French National Institute for Medical Research (INSERM), and a Lecturer in Molecular Oncology and Protein Science at the University Clermont Auvergne, France.

With all this said, when we talked over zoom it was morning in US Pacific North West and late afternoon in France: and yet Nina was cheerful, smiling, full of energy, eager to talk to our readers about her passion for science and medicine, as if the responsibilities she holds in her rich professional life were just a walk in the park.

Her research is focused on biomarkers discovery, looking for clues into cancer recurrence, which was the topic of our conversation.

NS: What is your background and your current role?

NRR: I was always interested in research, first in life sciences and then in medicine. Halfway through medical school, I met a professor of hematology and started working with his team, learning about that specific biology over the next five to six years. That experience convinced me to pursue the diagnostics of blood disease. Becoming a board-certified pathologist allowed me greater access to explore this field. My first specialty is hematopathology and from there I moved into the field of solid tumor oncology, focusing on female cancers (breast and ovarian). That led me to get involved in immuno-oncology biomarkers, working with NanoString, and exploring lung cancer. Lung cancers started being treated by immuno-oncology sooner than breast cancer, so I shifted my focus to that field.

NS: You were one of the first customers in France to use the nCounter PanCancer Panel in your research. How did you first learn about NanoString®?

NRR: In 2015, I was doing a translational study on breast cancer, looking for biomarkers of breast cancer recurrence. I met with a local sales rep for NanoString and I immediately recognized the advantages of this technology over other methods. I learned about the PanCancer Progression Panel, one of the research panels dedicated to metastasis so I decided to use that in my discovery study because markers of cancer recurrence were linked to metastasis. After that, I was enchanted by the technology and when the IO360 Panel came to market it was a logical decision to use it. We were approached by Dr. Pascal Morel because of our interesting cohort of lung cancers and suggested we use the IO360 Panel to look for predictive markers. Because I was already familiar with the technology and pleased with our earlier results, I did not hesitate to try this new panel.

NS: You are one of the experts on the IO360 Panel. You’ve used it to study immune checkpoint inhibitors (ICIs) and predictive biomarkers in lung cancer. How did the Panel help your research?

NRR: In many ways! The cohort of lung cancer tissue samples we had was comprised of biopsies; 30% were miniscule samples. I wanted to use the NanoString technology because classic RNA sequencing cannot be performed on such small samples. At that time, the field had only one biomarker, PD-L1, and everyone knows that PD-L1 is not perfect. When I saw what IO360 could assess- and it can assess so many cell populations and functional capacities within these populations – I really wanted to go beyond PD-L1. I wanted to see whether I could find more biomarkers because when it comes to immunohistochemistry with PD-L1; it’s not bad but it’s not perfect, either. We also didn’t have markers for tumor mutational burden in place, which are pretty complicated biomarkers not yet used in the clinic. I wanted to dig deeper into tissue immunology using these samples with the IO360 Panel. It definitely showed us things we couldn’t see with any other approach.

NS: With the IO360 Panel you’ve discovered different gene expression signatures in adenocarcinoma (AC) versus squamous cell carcinoma (SCC). Can you tell our readers what it all means?

NRR: We observed that the immune response against lung cancer in our cohort showed higher activation in AC and was more inhibited by reactive inhibition by PD-L1. SCC samples were much “colder” in terms of an immunological response. The first conclusion we published was that AC and SCC are two different diseases and that lung cancer is highly heterogeneous. It is difficult to separate one from the other, but we did discover some particular immune signatures that are characteristic of these two different diseases. I was thinking that in the future we have to examine larger cohorts of lung cancer and analyze them using both histology and the IO360 Panel to find subgroups within each histology that display a particular response to immunotherapy. Using IO360, we discovered a heterogeneity of two major histological types and biomarkers for those types. Our analysis is now more detailed, and we need to apply that additional analysis to achieve results in immunotherapy.

NS: Are these differences reflected in patients’ responses to ICI therapy?

NRR: Definitely. These are not simply histological differences; they are biological differences. The criteria used to distinguish between AC and SCC were based on histology even though we know the biology is different. Using biomarkers like those in the IO360 Panel, we found that some subgroups in AC responded better to ICI. More importantly, we discovered specific subgroups with AC that had very good responses and others that did not. The IO360 Panel lets us be more detailed and precise thanks to its additional biomarkers and signatures.

NS: The IO360 Panel comes with a Data Analysis Report that includes clear, concise data interpretation and publication-ready figures. How did you put this report to use?

NRR: We really couldn’t do bioinformatics and statistical analysis on our own, so the report was extremely valuable. We were happy with the scientists at NanoString we worked with and had a lot of confidence in them. We generated a great deal of data and are preparing now a manuscript that will heavily use those illustrations.

NS: With the advent of spatial biology we are learning that there a lot of different signatures within the tumor infiltrate and the microenvironment that may explain different responses to ICI therapy. Now that you have a GeoMx® system, what do you plan to do with it first?

NRR: We’re very excited for the installation and training. The first experiment we have planned will be on triple negative breast cancer, my major research interest. We’ll try to figure out what’s going on in these “cold” tumors. We have a much better idea of what’s happening in these immunologically “hot” tumors and we want to see if there’s a special, spatial relationship between the tumor cells and the immune cells. That might help us understand why a tumor is “cold” and if it will have a metastatic recurrence soon. We think that there are important clues in that microenvironment. We also have studies lined up to study breast cancer, another to study immunotherapy of head and neck cancer, and we’ll likely be using the IO360 Panel and the PanCancer Immune Panel. There is a big movement underway to study the microenvironments of cancers in different organs because it is known that immunotherapy doesn’t work the same across different cancer types. One of the reasons for those failures is likely due to the tissue structure and the spatial relationships between the tissue and immune cells. GeoMx will be the key to our understanding of those mechanisms. It will be able to see things we only dreamed about—it will be revolutionary.

FOR RESEARCH USE ONLY. Not for use in diagnostic procedures.

By Laura Tabellini Pierre
For research use only. Not for use in diagnostic procedures.