Q&A with Alexandre Reuben, PhD
We checked in for a quick chat with Alexandre Reuben, PhD, at the University of Texas MD Anderson Center for Cancer Immunology Research
Tell us how you came to be involved in immunological research?
I first became interested in genetics in school, but I really fell in love with immunology.
So what was it about immunology? Why is it so much more exciting to you than genetics?
I think being able to learn just how perfect our immune systems are at fighting disease – It just blew my mind. And to think we can figure out ways to hyper-activate the immune system to fight cancers – it’s mind-boggling. Immunology offered me a way to pursue a calling.
Why is that? What do you mean by, “calling”?
I was both intrigued and terrified by cancer. I felt there was just so much to learn and discover. I was in Montreal studying antigens and resistance mechanisms. It was solid learning, but really mechanistic; I wanted to have more direct impact on patients. I wanted to be in a translational / clinical setting. I was fortunate to have the opportunity to join Dr. Wargo's group at MD Anderson.
From Montreal to Houston! A big change!
Yes. I hate humidity and hot weather, so it’s a real testament to how exceptional MD Anderson is as an institution; I was thrilled to join this group. The work being done in Jen’s lab is really exciting; it’s a great group of people.
What is the focus of research in Dr. Wargo’s lab?
There’s a lot going on! Broadly speaking, we’re engaged in collecting serial biopsies from patients with melanoma and other cancers who are on targeted therapy and immunotherapy to better understanding their responses, and then working to develop novel strategies to combat resistance to treatments.
I’m new to the world of research, but I’m struck by the “ecosystem” of labs. Seems that collaboration and personalities are every bit as important as scientific “horsepower.” Is that your experience?
Absolutely! One of my early mentors explained it this way: 90% of the time in scientific research, you’re failing. So you better make sure you’re around people that you really enjoy working with. Jen and the team are terrific.
What are you working on now?
I’ve been looking at melanoma metastases with at least two different tumor types, and exploring tumor heterogeneity. The goal is to understand how they’re different and why they respond differently to different therapeutics.
It is, but like any question you ask in research, it leads to more questions (which is the fun part). Of the mutations that we studied, 50% are common or shared, but that means 50% are unique. So, part of the study is exploring whether tumor-specific mutations may be part of the immune response. Of course, this involves lots of immune profiling and that’s where Adaptive’s technology has been essential to our work.
What have you learned?
We’ve been surprised about the most striking differences in T cells: approximately 8% of T cells are actually shared in these heterogeneous tumors. That insight has potentially enormous implications for therapeutic treatment.
Explain more. Why was this a surprise to you? What are the implications of your findings?
We didn’t expect to find such massive differences. But it suggests different approaches which could be beneficial to these patients.
Well – I think these kinds of findings really open up the treatment possibilities. For example, it could mean potentially combining therapies to overcome different tumor resistance mechanisms, or targeting shared antigens or a combination of antigens. Currently only a single biopsy is studied to select the best treatment for patients, but if/when multiple biopsies are feasible, which is more often the case in skin cancer, this could help make more accurate decisions to treat not just one, but all tumors present in a patient. For example, clinicians could use combination therapies to both target the tumor directly and boost the immune response. Many have already begun using this approach. It’s pretty amazing.
Are you presenting at ASCO? On this topic?
I’ll be at ASCO discussing two different topics. One of the great aspects of Jen’s lab is that we are all engaged on multiple projects at once. It’s very different here: we each have a lot going on simultaneously because we are highly collaborative. I think this makes us better scientists, because we can produce more impactful work, rapidly. At ASCO, I will be presenting a poster looking into further studying these patients with multiple tumors, as well as a talk describing the results of a lung cancer T-cell profiling effort I was fortunate to inherit. The title of the talk is, “TCR Repertoire Sequencing of 254 Resected Non-Small Cell Lung Cancers to Reveal TCR Clonality in Normal Tissues Compared to Tumor Tissues”.
When you’re not working hard, what do you do for fun?
Well, my colleagues call me the “grumpy Canadian” so I’m not sure I’m all that fun! But sports were a big part of my growing up, mainly rugby and hockey, of course.
How’s the hockey in Houston?
Non-existent! But that’s ok for now. It’s been hugely rewarding being able to do work with the hope of positively impacting patients.
You can find Alexandre Reuben’s presentation at ASCO at 8:00AM on 06/04/2017, at room S406.
Alexandre and team are presenting a poster, Multidimensional Spatial Characterization of the Tumor Microenvironment (TME) in Synchronous Melanoma Metastases (SMM) to Yield Insights into Mixed Responses to Therapy in Metastatic Melanoma (MM) Patients, which will be presented on 06/03/2017, 1:15-4:45PM at Hall A (Poster Board 183, Abstract 9575).