Dendritic Cell Reprogramming for Cancer Immunotherapy

What have your Ph.D. studies focused on?

“My research has focused on bringing cellular reprogramming to cancer immunotherapy to overcome the current limitations of cancer immunotherapies, such as how cancer cells easily evade immune attacks and suppress the immune system. Solving these issues with cellular reprogramming was the goal.  

Our lab studies cell reprogramming: how to change the fate of cells from one specialized cell type into another. Previously, the group developed a way to generate dendritic cells in the lab, the sentinels of the immune system. These immune cells initiate immune responses against immune invaders like viruses, bacteria, and cancer. My project built on this by exploring whether we could use this dendritic cell reprogramming to reprogram cancer cells into dendritic cells, and in turn, use them to initiate immune responses against the cancer itself, almost like a Trojan horse.

We began by showing in vitro, that cancer cells could be reprogrammed into dendritic-like cells that present antigens, and activate other immune cells. This was the first step, and then as things in the lab worked, we continued moving along and asking bigger questions. Can we do this in mice? Can we vaccinate mice with these reprogrammed cancer cells that are generated in vitro and induce immunity against the cancer? 

We first showed that we can inject the cells itself, and that they elicit an immune response. However, as a therapy that would be very difficult to produce on a large scale. It would mean isolating tumor cells from each patient, reprogramming them in the lab, and making sure that the reprogrammed cells are the only ones reintroduced. As you can see the whole process would be very complex. After those scientific next steps were checked, we moved to the actual approach that we wanted to use and, in the end, we developed an in vivo gene therapy, where we reprogrammed cancer cells into the dendritic cells inside the tumor, within the immunosuppressive, cancer microenvironment.

We asked whether we could inject a virus itself into the tumor. The idea is that the cancer cells inside the tumor are hit with the virus, reprogramming them into dendritic cells and activating the immune system to fight the cancer. Doing this would avoid immune evasion by cancer cells. So, we set out to find the right vector, the right systems, and then test this on different types of cancer. In our most recent study, published last year, we showed that this gene therapy worked in mice.”

Your thesis cover is very artistic. Can you tell us more about it? 

“I wanted to create something that stood out. Science is full of creativity—whether in generating ideas, forming hypotheses, or designing experiments—but that creativity often becomes hidden behind standard plots and traditional figures. My thesis cover offered a rare chance to let that creativity show, by creating something artistic that could capture attention and spark curiosity at the first look.

The first thing that came to mind was Renaissance art. It is my favorite epoch of time, a period of intellectual “rebirth” when science begins awakening again from the Middle Ages. So, I decided the cover had to include Renaissance-style brushwork. While trying to determine what to draw, I started thinking about the dendritic cells at the center of our research. Where do these cells come from? Who discovered them? They were discovered by Ralph Steinman, who described them in the 1970s, as branched tree-like cells, naming them after the Greek word for tree “Dendron”. 

Since dendritic cells are well known for their “branches” or arm-like structures, I chose a tree as a metaphor, set within a dark forest. The surrounding trees symbolize the cold, suppressive tumor microenvironment. The central tree’s roots are intertwined like DNA, showing change from within, while fireflies circle around it. These fireflies represent immune cells such as B cells and T cells, bringing light into the darkness as they move toward the tree.

To create it I used AI, using what I call ‘AI inception.’ I carefully wrote a prompt, asking ChatGPT to give me a prompt for the AI image generator, Midjourney. I selected one of the images it generated and adjusted it to be more along the lines of what I wanted. The prompt itself became my thesis cover description, so anyone can reuse it to generate their own version. The cool thing is that the AI will never generate the same image, it will always come up with something else, like an artist not being able to create the exact same concept in the same way. My favorite part about the cover is that everyone interprets it in their own way—and each interpretation is original and inspiring.”

How did you end up doing your Ph.D. in Lund?

“As a child, I was always interested in science and the animal kingdom. I was the kid catching insects, and lizards, and making observations about them. At the University of Vienna, as a bachelor’s student I joined the general biology program. I needed to take courses in botany and anthropology before selecting my major and focusing on what I was really interested in, microbiology and genetics.  

I stayed at the University of Vienna to do my master’s studies in molecular biology. During that program, there was this subject on molecular medicine, which really started gearing my interest more towards the medical sciences.  When I was applying for master’s thesis projects, I started looking online for institutes that focused on molecular medicine and came across the Wallenberg Centre for Molecular Medicine’s website where they described Filipe and the lab’s research. It seemed like the perfect fit for me, so I wrote to him, and he replied. 

When I had the interview with Filipe, we met, and he explained the project to me. I was immediately hooked. I thought to myself, “Ok this is first of all, a very cool, innovative approach.”  It really captured my interest with the out-of-the-box thinking and out-of-the-box methods. Secondly, it was my area of interest, it was cancer immunotherapy. Before that I worked a bit with cancer therapies in labs as a bachelor student and knew that I wanted to get into this field. I had also worked with gene therapies, so this project combined my previous experiences with my interests in cancer research. I decided to do my master’s project in Filipe’s Lab. Then after that, he offered me a PhD position, and I accepted. I wanted to stay, to continue the work and do my PhD studies with the lab.” 

What have you enjoyed most during your Ph.D. studies? 

"Many things really, and that’s a good thing. Now that I have been writing the acknowledgments section, it’s quite easy to think of the main thing which is simply being with the people in the lab. It is always the environment that makes something good or bad because you can have the best research but if you’re not having fun with the people around you then nothing is fun. It's always the people that shape the mood, the environment. So really, the most enjoyable part of my PhD studies was the environment and everyone that was around me. 

I even dedicated the thesis partially to them because they not only were my colleagues, but they became my friends and in a way family. You spend all your time with them for five years; they saw me much more than my parents or even my girlfriend and friends back in Vienna.  In my case, our time together was extremely enjoyable, we had so much fun both inside and outside the lab. 

Of course, there are also certain findings that come along, where you have this result that you hoped would come out of the experiment or something that is completely surprising. These surprises are what make you really excited about science again.  And they help during the difficult times when you're doing one experiment after the other. It's hard work, you get tired and exhausted, but then when you reach the end of an experiment and there is a result that is surprising and exciting, you just forget all about these hard times and you're all in again. Ready to find the next discovery.”

What has been the most challenging aspect?

“The most challenging aspect as a PhD student is how many different types of tasks you have to do, all at the same time. This might depend on how ambitious you are as a student, and the expectations of your supervisor, but generally as a PhD student today it is expected that you know how to do experiments, how to present, how to write, how to create art. Juggling how to do all of this together is really challenging, especially when you are working within a limited time span, because your time as a PhD student does eventually come to an end. I mean you can take your time, but you are expected to be done within the timeframe of the deadlines you’ve been given. 

On the other hand, it’s also positive. You get trained in everything, and that's why a PhD is so valuable, because you show that you can do all these things.”

What advice would you give future Ph.D. students? 

“First, align your expectations with your PhD supervisor very early on in the process. The relationship between you as a PhD student and your PhD supervisor is important. My supervisor, Filipe and I, for example, had a really good relationship throughout because our expectations of each other were aligned early on, making my PhD an enjoyable time. In cases where expectations might be misaligned or mismatched, that can add an extra layer of difficulty to the PhD. 

Second, I recommend putting together a priority list when setting out to look for a PhD position. There are many PhD students that don't have a good time during their studies because they are not a good fit with a lot of parameters: the project, the lab environment, colleagues, project supervisors, country, culture, salary, etc. These are all parameters that need to fit you as a student, as a person. It will never be that they are all a perfect match. For some people, the supervisors or the university will be most important, for others it will be the project itself. Some might prioritize having more freedom to explore and learn on their own, while others might prioritize having a supervisor who can help with everything along the way. These are different approaches, and you need to reflect on what you want and what will suit you best to help you succeed. That requires that you really know yourself, your character, and that you stay true to yourself throughout the process. 

Lastly, do not immediately jump blindly into a PhD directly after your master’s, just because you want to do a PhD. I would recommend first being in the lab for some time. A lot of people, including myself, think they want to do a PhD immediately after getting your master’s degree. But I would really recommend taking the time before, whether during the Master’s or a fellowship, to see that the research group is the right place to do a PhD for you as a student and a scientist. Is this what you really want to do? Is this the right environment to do it in to successfully complete a PhD?  

What does it matter if you start a year later? Not much will change if you wait, and that extra time in the lab can be used to jumpstart your PhD. It is time that you can generate data or start creating a network within your field of interest. And if you figure out that a PhD is not what you want to do, or that the lab is not the right fit for you, then you know it’s time to move on. You can add that experience in the lab to your CV which can make it easier when applying for new positions.”

What are your plans following your Ph.D. defense?

“I'm starting a postdoctoral fellowship starting in October. After five years of living abroad I’m returning home, where my family, girlfriend and my friends are. I also want to go back to Vienna because I want to become a Principal Investigator (PI), either in academia or industry, and to achieve that goal, I need to do a postdoc first.

Now following my own advice, I wanted to prioritize the environment I would be in. Two years ago, I was at a Cancer Immunotherapy Winter School in Vienna where I met Barbara Maier, a former postdoc in Miriam Merad’s group, who has established her own research group in Vienna.

We chatted and she seemed very nice and that she could be a great mentor. In February, I wrote to her that I was interested in doing a postdoc and the possibility of training in her lab, and I sent along my CV. She replied positively and invited me for a meeting where we aligned expectations, and I got to meet people in the lab and see the environment. Again, she seemed very nice, her students and employees seemed very friendly, and I walked away with a very good impression of the lab. After that, I officially applied and went through the full interview process. So now I’ll be joining Barabara’s lab this October as a postdoc within a pre-ERC postdoc program.

If everything goes well, my new postdoc project will merge two fields: cancer immunotherapy and neuroscience. We want to know how cancer affects the behavior of model organisms, like mice, through the immune system interactions. It's exciting, not only because of what we might find, but I’ll also be stepping into neuroscience for the first time. I’m looking forward to extending my field of expertise.”

Any final thoughts? 

“I would like to include a message to all the PhD students, not only in Filipe's lab, but also in the other groups at the Lund Stem Cell Center. I made a lot of friends there, too. I want to wish them all the best for their PhD studies. I hope that they all make it to the finish line happy, still excited about science and ready to follow their dreams and goals. And I want to remind them not to give up,” concludes Ervin.