Conversations with experts: Immuno-Oncology
April 15, 2024
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Massimiliano (Max) Mazzone is a group leader of the Laboratory of Tumor Inflammation and Angiogenesis at VIB-KU Leuven Center for Cancer Biology. He is also professor at the KU Leuven Department of Oncology at the Faculty of Medicine. Karin de Visser is the group leader of the Inflammation and Cancer group at the Netherlands Cancer Institute (NKI) and Oncode Institute, and a professor at Leiden University. Join us in this double interview, where we discuss their shared passion for immuno-oncology, their research, the upcoming Immuno-Oncology conference, and much more.
Hello Max and Karin. Thank you so much for taking time from your busy schedules to talk to us. You both work in a very similar research field, but could you specify what your current research focuses on?
Karin: The overall goal of my team is to improve immunomodulatory strategies against metastatic breast cancer. The effectiveness of current immunotherapies remains modest in breast cancer patients. We want to gain new insights into how the immune system influences the metastasis process, using pre-clinical models and with our primary focus on breast cancer. We studied the involvement of myeloid immune cells in the efficacy of immune therapy responses. We also became interested in studying the mechanisms underlying inter-patient heterogeneity in the composition and function of the immune system. There are different genetic drivers of breast cancer, and this could mean that the immune landscape between patients with different mutations in their tumors has a different composition and, therefore, will be activated in different ways. These insights might help us move towards more personalized and efficient cancer treatment strategies.
Max: The main focus of our research finds itself in the tumor microenvironment (TME). In the past years, we have gradually discovered that the key to more effective cancer therapies might lie in the complex structures surrounding cancer cells. We are looking into ways to fight tumors by allowing immune cells to overcome nutrient starvation and competition in this microenvironment so that these cells of the immune system can attack the tumor, and immunotherapy can better work. In my lab we are particularly interested in macrophages as part of our immune system. We want to understand their metabolic interplays and attune them. For example, we can make the macrophages “steal” sugar from the cells forming the tumor’s blood vessels, preventing cancer cells from spreading.
What inspired you to build a scientific career in this field of research? Were there any personal or professional key moments that sparked your enthusiasm?
Karin: My fascination for immune-oncology came during my years as a master's student. I read a book by Dr. Steven Rosenberg, the founding father of immunotherapy. In his book, he talks about dealing with his patients, his early experiments with NK-cells he grew in the lab, and his rare successes and many failures. This is where it all started for me. At the beginning of my research career, I mainly focused on T-cells. I noticed something in the tumors was blocking these T-cells. This bridge between cancer biology and immunology truly fascinated me.
Max: Here, I can give a very specific answer (laughs). I remember a paper in Cell in 1997 by Folkman on Endostatin. In this paper, endostatin is described as an angiogenesis inhibitor that also potentially inhibits tumor growth. My background is in the field of vascular biology, so this intrigued me. And my fascination only grew. I was lucky to meet people who work on macrophages and vascular biology interactions. I started to focus on macrophages myself, and like this, I rolled into the world of the tumor microenvironment and cancer immunology. The rest is history.
Of course, we all have our personal stories as well. When I was just 18 years old, my mother was diagnosed with metastatic breast cancer. She was a survivor for two times. Nevertheless, this was a rough period at that time, being so young. But in the end, it pushes me to try and bring new drugs from the bench to the bed side and help people.
Karin: Almost 1 in 2 people will deal with cancer in one way or form. In my family, there is hereditary breast cancer. Like so many people, I also understand the impact this disease can have on whole families.
There are many research centers worldwide working on cancer and immunology as well. How important is it for your research to maintain a strong scientific network? Do you often collaborate with peers in the field?
Karin: It is essential! There is such a huge amount of expertise and technologies that it is simply impossible to do all the research yourself. Cancer is just too challenging. We will not solve this disease individually, so we must work together. Actually, the TME is a good example to prove my point. This field of research was non-existent 20 years ago, and now research groups like the one from Max are doing incredible findings. Another example is immune checkpoints. The identification of these molecules did not even come from cancer research. It shows that collaborations with people in different fields are very powerful.
Max: Yes, I totally agree. Cancer is just too complex so solve in one field. We will need all the help we can get. From bio-informatics to biologists, chemists, bio-engineers, biomedical scientists, clinicians, and many more. We will need each specialization to solve the puzzle. In June, I will join the first conference organized in Denmark by the Europen ImmunoMetabolism Network (EIMN). This is a great way to foster new collaborations, and pool together knowledge. I am a firm believer that this makes us better scientists.
Speaking of the importance of a scientific network and conferences. You are both members of the organizing committee for the upcoming VIB conference on Recent insights into immuno-oncology. What is the importance of conferences in your scientific career and maintaining this network?
Karin: Conferences are of huge importance. They have the power to let you critically look at your own research, and sometimes, they can even change the direction of your science. Several researchers in my lab join these conferences, share expertise, and exchange contacts with peers to continue the discussions. Poster sessions are one of the favorite components of a conference. The feedback you get by presenting your unpublished data and research can result in new ideas.
Max: yes, for sure. Especially for younger researchers it is a great first step to build their network and also get some feedback on their work. Besides that, it is also a good opportunity to discover what next steps to take in your career, like a post-doc for example. During COVID-19, when conferences were online, I could not concentrate for longer than 1 hour. I really need this personal interaction and deep diving into research with someone. I’m happy the live conferences are back.
Do you have a speaker or topic you particularly look forward to hearing more about?
Karin: If I may say so, I think we put together a great schedule of speakers covering a wide spectrum of topics. If I had to choose one thing, I would say I’m very excited about the new topic of glycobiology in cancer. This topic was suggested based on the feedback from last year’s conference.
Max: I agree, I am also looking forward to hearing more about glycobiology. Besides that I am also excited for the CAR sessions (CAR-T, CAR-NK, and CAR-Macrophages). Finally, I also think we made quite an effort to promote not only young speakers, but also encourage young researchers to present their posters. It’s going to be nice to hear from them as well.
Karin: Yes indeed. I am also looking forward to seeing the posters of the new generation of researchers and seeing the upcoming science.
Max: Maybe on a personal note, I’m also looking forward to hearing from Mathias Wenes. He was one of my PhD students, now working at the University of Geneva. I will be very proud when sitting in the audience listening to his presentation. (laughs)
Looking further into the future, where do you think the next breakthrough in your field lies?
Max: Well, like we mentioned before, solving the puzzle of cancer will need the effort of many people in many fields. So, I don’t think there will be one big breakthrough. There will be advancements in many fields. Something that is coming up massively, according to me, is RNA vaccination against cancer. Adapting these RNA vaccines to fit the genome and mutations in patients better will be a big thing.
Karin: To elaborate on that, I think we will see more personalized immune intervention strategies. Now the rule is: one size fits all. I predict a more personalized strategy will benefit patients not responding to current treatments. I also think we will find a way to engage myeloid immune cells in therapies instead of blocking them. They are in fact, the biggest army in our immune system
Max: Very true! These answers are again a testimony of how different insights can reinforce each other and why it is important that scientists work together. We could treat patients with therapies based on both ideas. If we look at cancer from different angles, we could really help patients even more efficiently.
Do you have any good advice for young scientists, students even, who have the ambition to step in your footsteps and want to build a career in immuno-oncology research?
Karin: Follow your heart and your passion. It really needs to be a passion because you will spend a lot of time on your research. Be confident in your data as well. As we said earlier, 20 years ago, some fields of research were still non-existent. And look at us now! We have a whole network of passionate scientists who are working together in the field of immuno-oncology, and we are at the forefront. Again, this is a testimony to building a good network.
Max: Being at the forefront also comes with challenges. Although people talk about exact science, it is rarely precise science. Nine out of ten experiments will fail, but the key is to stand back up, learn from mistakes, and keep believing in your project. Don’t give up and be resilient.
Karin: You can also find beauty in failing. It is a part of your scientific freedom. You are allowed to try new things, be innovative, and break barriers. And failing is part of this.
Max: True. It really is a privilege to be able to do this research.
