2024 is the University of Chicago Medicine Comprehensive Cancer Center’s 50th anniversary of National Cancer Institute designation, thus we are planning a year full of events to honor our past, communicate our present, and envision our future. Cancer Luminaries is our podcast to learn more about the lives and careers of our Alumni Stars Lecture Series’ invited guests.
Episode 6: Dr. Stefani Spranger on Moving the Field Forward
Host Camilla Frost-Brewer gets to know Alumni Star and cancer immunologist Stefani Spranger, PhD, Associate Professor of Biology at the Koch Institute for Integrative Biology at MIT. Dr. Spranger studies how the body’s immune system interacts with growing tumors to harness the immune response to fight cancer. In this episode, she recounts how a mind-blowing paper led her to a career in cancer immunology and the advantages of being an immunologist surrounded by cancer biologists and engineers. She also talks about the collaborative nature of scientific research in the United States, the joy of seeing a mentee blossom, and learning to trust that you are doing enough at home and at work.
Transcript
[00:00:00.260] – Camilla Frost-Brewer
Hello, listeners. This is Camilla, your host for Cancer Luminaries. I’m very excited today to be with our special guest, Dr. Stefani Spranger. Thank you so much for joining us.
[00:00:13.460] – Dr. Stefani Spranger
Thanks for having me.
[00:00:14.690] – Camilla Frost-Brewer
Awesome. So we’re just going to get started, and I could never do a full introduction justice. So if you will introduce yourself to our listeners, and if you feel comfortable, can you maybe share with us what made you want to become a cancer researcher?
[00:00:29.030] – Dr. Stefani Spranger
Yes. So let me first start out with an introduction. I’m currently an associate professor at MIT, specifically there in the Cancer Center, which is called the Koch Institute for Integrative Cancer Research. And also the biology department. The difference between MIT’s Cancer Center and UChicago’s Cancer Center is MIT’s is not comprehensive, so we’re only basic science-oriented. For my background, I am originally from Germany. I did my PhD in Germany and then moved to the University of Chicago to do my post-doc with Tom Gajewski here in the Cancer Center. And the reason why I became a cancer researcher/immunologist, which I actually consider myself, was a paper that was published in the mid 2000s by Steve Rosenberg’s group. And that group showed that when you take tumor cells surgically, you resect them, you chop them into small pieces, and then you culture the T cells, so a part of our immune system in cell culture, grow those T cells up to really large numbers, and then transfuse them back. In a fraction of patients, the cancer just went away. And that, to me, was mind-blowing, and I wanted to understand more of how we can leverage our immune system to fight cancer.
[00:01:52.930] – Camilla Frost-Brewer
Wow. One paper changed your life. That’s amazing. If anyone in that group who is a part of that paper is out there, way to go. You did it. So congratulations on being an alumni star for UChicago Medicine Comprehensive Cancer Center for our 50th anniversary seminar series. Can you maybe just tell us about when you were at UChicago, and you shared you were in Dr. Gajewski’s lab, but what did you do there as a postdoc?
[00:02:21.770] – Dr. Stefani Spranger
So I joined Tom’s lab with the background of mostly human immunology and cancer biology. And his lab is mostly focusing on preclinical mouse models. And when I joined, it was a steep learning curve on mouse immunology and how to work with mice and how to do all of those preclinical models. But I contributed to understanding why tumors actually have those T cells in them. That was the first observation that we made in the lab. And then figured out why tumors actually and how tumors kick those T cells out. Because from the cancer cell’s perspective, you don’t want those T cells to be around, because if you have them, there’s a potential that they can recognize something on the cancer cell and then actually kill the cancer cell. And that’s bad if you are the cancer cell. And by understanding more about how tumors actually kick immune cells out, we can hopefully understand more of how we can get them in via therapeutics.
[00:03:24.130] – Camilla Frost-Brewer
Wow. That’s no small feat. I mean, to learn about mice models, mouse models? Mouse models. Interesting that it’s not plural. Anyway, to learn about mouse models and then to contribute to such a significant finding, what was that like as a postdoc?
[00:03:40.460] – Dr. Stefani Spranger
It was very gratifying that you piece the individual pieces that you do through your postdoc together, and they actually accumulate to a really large chunk of work that is still being recognized and has impacted a lot of other labs to actually do research on other cancer types and along other their pathways and found similar traits in other cancer models. So now there’s an even larger body of work collectively through multiple labs that show a similar phenotype is true in different cancer types. And I think it allows the field as a whole to move forward and understand the tumor-immune interaction more mechanistically.
[00:04:20.780] – Camilla Frost-Brewer
That’s fascinating. So moving into our next question, but I’m also just very curious, can you talk to us about what you do now? What does your lab look look like? What research do you participate in? And you said you considered yourself an immunologist. Talk to us about how that factors into doing research, maybe through a cancer center.
[00:04:41.380] – Dr. Stefani Spranger
Yeah. So I joined MIT’s Cancer Center as one of maybe three immunologists or people that focus on the immune system to fight cancer. So I’m embedded with a lot of very hard-carrying cancer biologists, which I sort of did on purpose because I want this interaction. But I always think more about what is wrong with our immune system, what is not working appropriately so that the immune system is not recognizing the cancer. So it’s just a slightly different perspective that I bring to the table on asking, why is it not working in this patient, but it is working in this other patient population. And with that lens, we took a broad look at in which cancer types do we have immune responses and which cancer types does immunotherapy currently work? And then we built comparative models where we model not necessarily the cancer cell biology, but the immunology that is at play in those patients, and then try to figure out what is the difference in the immune cascade that is happening when the immune response is productive and can eliminate cancer cells, and when the immune response is not productive.
[00:05:49.090] – Camilla Frost-Brewer
Yet again, nothing small. Gosh, I’m so interested. Can you maybe share with us some things that you found to be significant or quote, unquote, true? What kind of cancer types do you see immunotherapies working better in?
[00:06:08.230] – Dr. Stefani Spranger
Yeah. So one of the cancer types that we focused on really early was non-small cell-lung cancer. And clinically, that’s a really interesting cancer type because we see all the different shades of gray when it comes to immune responses. We have a fraction of patients that currently have a really good immune response. They respond to immunotherapies, and they have long lasting benefit, clinical benefit from it. And then you have patients that you could do anything to, and they will still succumb to the disease. So there’s also a huge unmet need. And we have correlative studies in this disease, clinically. But we really don’t know and understand the immunology behind it. And one phenotype that really intrigued us is there is a fraction of patients in non-small cell lung cancer that have those T cells present, but immunotherapy doesn’t work. So we wanted to build a model to understand why are these T cells that are sitting in the tumor not working as the same T cells that sit in another human in another cancer that are working. And we figured this out by putting the same cancer cell line either in the flank of mice or in the lung of mice.
[00:07:21.410] – Dr. Stefani Spranger
When we put the same tumor cells in the flank, they’re responsive to immunotherapy. The T cell response looks very productive. They have all the effector molecules that are needed to kill cancer cells. Versus if we look at the T cells in the lung and we can fix all various parameters so that they’re as similar as we can make them, the T cells are incapable of killing the cancer cells. They don’t have the molecules required to do so. And then we figured out this is actually not a consequence of the tumor itself. It’s imprinted in the T cells when they become activated in the tissue-draining lymph node. And that set us out on a quest that every tissue has its own network of immune constraints. And by understanding these immune constraints specific to each tissue site, and by extension to each cancer type, because each cancer grows in a different tissue, hopefully we can not personalize, but target immunotherapies closer to the cancer that you actually want to treat.
[00:08:18.770] – Camilla Frost-Brewer
I have to say, as a non-scientist, non-researcher, if you will, that makes perfect sense. No notes. That makes perfect sense. And I really love the way you phrase it, that your lab has set out on a quest. You don’t know maybe where the endpoint is or where it’s going to lead you, but you know you’re going towards something, and I really appreciate that. So my next question. You said you’re from Germany. You did undergrad and your graduate degrees there, and then you came to UChicago and the States for your postdoc. One, I’m curious, had you ever been to the States before?
[00:08:53.640] – Dr. Stefani Spranger
I’ve been to Massachusetts and Florida on a family vacation before. Before. And then here, we talked about this at dinner last night, during Snowmageddon.
[00:09:05.570] – Camilla Frost-Brewer
No, in 2011?
[00:09:07.910] – Dr. Stefani Spranger
Yeah, that was when I interviewed for the postdoc.
[00:09:10.590] – Camilla Frost-Brewer
Wow, what a dystopian way to interview. And you still came here. Thank you. I guess it only got better from there? So how did being here influence your career trajectory?
[00:09:27.470] – Dr. Stefani Spranger
Oh, I think it was a pivotal point because being introduced to how provocative you think about science in the States and how also collaborative the community is as a whole, I think there’s much more cross-talk between institutions and also within an institution. There’s much more collaborations that you see compared to Europe. It’s, to me, far less of a single person driving the science, but much more about this is a collective effort to actually make an impact and help people to not succumb from this horrible disease.
[00:10:03.170] – Camilla Frost-Brewer
Yeah. I sit in the Cancer Center, and I hear all of these funding opportunities for team science awards. And I think that goes to, it really is a collaborative effort, not just in the Cancer Center, but people who maybe aren’t members, people who are at different institutions who have since left UChicago, but still do really important work in cancer biology, immunology, et cetera.
[00:10:28.890] – Dr. Stefani Spranger
I think I will take many disciplines. In the Cancer Center at MIT, because we’re a technology-focused institution, we have a lot of engineers. And I really appreciate their mindset because the moment you tell them what the problem is, they’re trying to figure out a solution. Yes, so true. And that’s amazing. As biologists, we’re trained to find problems. We’re not trained to find solutions.
[00:10:54.120] – Camilla Frost-Brewer
But were there any key moments, maybe from or things you learned at UChicago that you carried with you throughout your career to MIT? And maybe does it show up in your current position or how you run your lab?
[00:11:07.570] – Dr. Stefani Spranger
I think something I really learned throughout the process of publishing papers here was to identify what is a publishable unit. So to see early on, okay, this will be the vision of the paper. This is the work that we have to do to get to that point. And don’t necessarily obsess about all the nitty-gritty details in the beginning, but see the storyline through and then fill in the blanks. So that’s a mentoring style that I try to give on to my mentees, that sometimes it’s important to do this very last experiment because you want to know if it works, and then you go back and fill in the blanks. You don’t necessarily need to go chronological. I think other pivotal moments were I worked here with a really talented undergrad who’s now… She must be finishing med school right about now.
[00:12:02.380] – Camilla Frost-Brewer
Excellent.
[00:12:03.160] – Dr. Stefani Spranger
And she joined the lab as a rising sophomore and was very shy, had no self-esteem on doing an experiment, very insecure. And she graduated from UChicago, still being in the lab running small mouse experiments all by herself. And seeing that growth and contributing to maybe a little bit shaping the way she thinks made me really excited about mentoring. And it’s still something that gets me through all the setbacks that you have as a PI. You don’t get a grant, a paper gets rejected. There’s plenty of setbacks. But when you see a grad student starting out and they come with so many questions, and for everything, they need reassurance. And towards the end of their graduate career, they’re like, No, we’re going to do this. I know this will work. This is right. No, you’re wrong. And seeing that growth in a person is something very gratifying.
[00:13:02.900] – Camilla Frost-Brewer
Yeah. I think that I resonate with that sentiment. I think that’s why I started off my career working with undergraduate students, just to see…. It’s such a pivotal time in life to go through an undergraduate degree. Can you talk to us about what type of mentoring you do? Is it through your lab, through a volunteering situation?
[00:13:29.370] – Dr. Stefani Spranger
So we have multiple levels. I have currently seven grad students in my group. So there’s a lot of mentoring through grad students in the group. Then we also have a graduate committee, of course, for the grad students for the entire program, and I’m sitting on that. And through that extent, I’m mentoring the first-year grad students until they actually land in a lab. And then at MIT, we also have undergrad advisees. So I also see roughly five to six undergrad advisees that come in sophomore year all the way through their senior year. And you really see their personality because I only meet with them three times a year. But you see their personalities change, and they have no idea of what they want to do in life to, Oh, no, I’m going to do this and this and this. And then I also teach. I teach an undergrad and a grad class at MIT. So there’s plenty of mentoring.
[00:14:22.840] – Camilla Frost-Brewer
Yeah. No, that’s amazing to be such a prolific researcher as well as a really accomplished mentor and educator. That’s phenomenal. This is a really broad question. I’m warning you. Where do you hope to see cancer research, care, discoveries, or advancements go in the next 50 years?
[00:14:44.900] – Dr. Stefani Spranger
Oh, you’re giving me a big time frame.
[00:14:47.060] – Camilla Frost-Brewer
I know, because looking at the past 50 years… We came far. We came far.
[00:14:51.990] – Dr. Stefani Spranger
So I think the biggest advance that I see that isn’t quite there yet, but I think we’ll get there, is early detection. Understanding how we can use cheap but reliable screening tools that can be done at home or at the primary care physician that show an elevated risk that there might be cancer and then do a more deeper screening, together with surgery and early, very safe immunotherapies. I think that combination could make a really big dent in how many people actually suffer from cancer, because at that point, it would be a minimal surgery and maybe a vaccine. And that doesn’t impact your life all that much, but it can give you 20 years. I think we’ll also make advances in treating late-stage cancer, but it’s a really hard ask, right? You have billions of cancer cells that are disseminated, and there won’t be one cure that will solve this all. I think if we focus or put a lot of effort into early detection, surgery, and neoadjuvant and adjuvant therapy, I think we can actually make a huge impact in many people’s lives.
[00:16:01.880] – Camilla Frost-Brewer
I love that. I think that’s really optimistic, but also realistic. Early detection. I feel like other alumni stars have mentioned this, that early detection and community trust and education are going to be real game changers.
[00:16:18.790] – Dr. Stefani Spranger
Yes. And I really think I certainly have much more of a basic research perspective, but I can see that community trust and reaching out to people that have more hesitation towards medicine will be a key feature because something I see at MIT is there’s a lot of urine tests that are being developed that can actually pick up proteins that are being secreted from cancer cells. But you need the people to actually do those tests if they are available. And yes, the big problem is there are some false positives. So you will get a positive signal, and then the answer will be, well, you don’t have cancer yet. But from my perspective, it’s still better to then be screened.
[00:16:57.310] – Camilla Frost-Brewer
Right. It’s still better to know and to consistently check in with the doctor every few years. Like, okay, was this a false positive? It’s like other medicine and preventative measures that we have to go to certain… Do certain tests every three to six years, right? To make sure we don’t have something bad.
[00:17:15.420] – Dr. Stefani Spranger
Yeah. It’s like going to the dentist, right?
[00:17:17.510] – Camilla Frost-Brewer
Oh, yeah. Okay. I was thinking way more internal, but yes, dentists also works. I also think a really key factor that you mentioned was bringing in primary care physicians, being able to do cheap tests, send patients home with a test to then report back. There are so many people who trust their primary care physicians, but maybe don’t know, don’t have a cancer biologist in their family, don’t have somebody who works at a hospital to say, Yes, go get screened. They’re like, okay, I trust my primary care physician. I will do this test.
[00:17:53.950] – Dr. Stefani Spranger
Yeah. And I think if it doesn’t require the primary care physician telling you to then schedule a meeting with the specialist, that’s another hurdle you have to take. It has to be as easy as a blood draw that you can do in the primary care physician’s office or at home, and then be, Okay, this is the result. And then if it’s positive, then, of course, you need to go to a specialist.
[00:18:16.180] – Camilla Frost-Brewer
I have a very silly question. We have a few minutes, so I’m going to ask it. This is so specific. So some of those models that are looking for certain proteins in urine, is there any connection to the research being done with dogs who can sniff out… I don’t know if it’s proteins, I don’t know what it is in urine, but they can smell cancer in urine?
[00:18:39.170] – Dr. Stefani Spranger
So the test I was thinking about, you actually get nanoparticles. They’re either orally, so you take a pill or you get a small injection, and then you read out the same nanoparticles that come through the urine. But I’m certain that hormonal changes that we just don’t understand yet could be detected as well in the blood or the urine. And this is much more likely that dogs actually sniff that. And yeah, I think… You sometimes know that something’s off with a person if they’re sick, but the person doesn’t even know they’re sick. So probably even other humans have a sixth sense of something’s off.
[00:19:19.440] – Camilla Frost-Brewer
Interesting. I love this aspect of the unknown. I also just really trust animals when they say things are wrong. So my last question is, you’ve been very successful in your academic career, professional career. Reflecting on maybe how you got to this point, is there anything in your personal life or anything you’d like to share or any advice you have for young investigators on ways to balance your professional career and personal life?
[00:19:48.910] – Dr. Stefani Spranger
I think the best advice I could give people is you can do it, even if you think you can’t. And there will never be a perfect time. We had our kids when I was faculty, but in hindsight, we probably could have make it work during post-doc as well, because, yeah, you will never have enough time to actually balance personal life and professional life perfectly. That time doesn’t exist. And I think just believing in yourself and doing it and trusting that you’re doing enough in both worlds is essential. To have that inner strength to tell yourself, Oh, I’m doing enough here and I’m doing enough there. And the trainees will survive if I’m not there on a Friday afternoon. And the family will also survive if I have to work a Saturday morning. It’s going to be fine.
[00:20:39.490] – Camilla Frost-Brewer
Yeah. Once again, very realistic and optimistic. You can do it.
[00:20:44.900] – Dr. Stefani Spranger
Yeah. I really think everybody needs to find their own path and their own working rhythm on how they actually make it work. Some people get up really early. I’m not a morning person.
[00:20:55.030] – Camilla Frost-Brewer
Me neither.
[00:20:55.680] – Dr. Stefani Spranger
I, for instance, often work until midnight because I am much more productive working after the kids are in bed. But everybody has to find their own rhythm on how they actually get the stuff done. Be comfortable with it. I think that’s the key element. Find your own path and then stick with it.
[00:21:14.280] – Camilla Frost-Brewer
Yeah. Awesome. Thank you. Well, thank you so much, Dr. Spranger, for joining us today. It has been such a pleasure. All right. Have a great day, everyone.
