E. John Wherry, PhD, Receives 2023 AACR-CRI Lloyd J. Old Award in Cancer Immunology

E. John Wherry, PhD — the director of the Institute for Immunology, chair of the Department of Systems Pharmacology and Translational Therapeutics, and the Richard and Barbara Schiffrin President’s Distinguished Professor at the University of Pennsylvania Perelman School of Medicine—has received the 2023 AACR-CRI Lloyd J. Old Award in Cancer Immunology. Named in honor of CRI’s founding scientific and medical director, this award recognizes an active scientist whose outstanding and innovative research has had a major impact on the cancer field and has the potential to stimulate new directions in cancer immunology.

Dr. Wherry’s relationship with CRI goes back two decades, when he was first funded as a CRI postdoctoral fellow in 2000 while working in the Emory University lab of Rafi Ahmed, PhD. During that time, he made several important discoveries. Most notably, his work provided some of the first evidence that blocking the PD-1 immune checkpoint can enhance immune responses against viruses, which paved the way for the development of anti-PD-1/PD-L1 checkpoint inhibitors against cancer.

After completing his CRI fellowship, Wherry launched his own independent lab, first at The Wistar Institute and then the University of Pennsylvania, where he’s continued to advance the frontiers of immunology. Overall, his research — including more than 220 peer-reviewed papers that have been cited more than 90,000 times — has had profound implications for our understanding of the immune system and ability to treat cancer and COVID-19, among other diseases. During his time at the University of Pennsylvania, Dr. Wherry, who is now an associate director of the CRI Scientific Advisory Council, has also sponsored four CRI fellows of his own: Kristen Pauken, PhD (2014-2016), Mohamed Abdel Hakeem, PhD (2016-2019), and Josephine Giles, PhD, (2018-2021), and Simone Park, PhD.

We spoke with Dr. Wherry in advance of his Lloyd J. Old Award Lecture, which was given on April 17 during the 2023 AACR annual meeting.

What does this award mean to you?

I’m truly humbled and honored. It’s really an incredible feeling to win this award. I was originally a CRI postdoctoral fellow, have been involved with CRI since early 2000 or 2001. It’s just a tremendous feeling of gratitude and support from CRI and from AACR to have our work recognized. We’re doing something that we hope matters for patients and science in general.

What is ’immune health’ and what is its role in cancer immunotherapy and medicine?

Immune health is really the idea that each of us has a distinct immune system, immune fingerprint, and really immune characteristics because of our own unique immune history. We can think that genetics impacts a lot of our biology, but actually, the immune system remembers all of our previous immunological encounters from our lifetime. Those previous encounters impact our future responses. If we can characterize that individual immune fingerprint, we can think about not just personalized medicine, but personalized immunotherapy. Taking advantage of one’s own immune system and immune characteristics to really design treatments that work just for that individual. We often see in clinical practice that there are places in cancer immunotherapy and in autoimmunity where you have what we call clinical equipoise, where you have a choice of different drugs or really don’t have data on how to make the choice between those drugs. We envision immune health as being able to use the immune system to help make those decisions in a way that’s right for that individual patient based on the way their immune system has evolved over their lifetime.

What science are you most looking forward to at AACR 2023?

I think there’s a lot of interesting stuff to look forward to at AACR this year.  We’ve seen an explosion in our appreciation for immune ecosystems in tumors. The idea of spatial organization of immunology in the tumors, and even in the lymph nodes is really changing the way we think about cancer immunotherapy. Second, I think that we’re seeing continued advances in being able to engineer and access the immune system in new ways. Whether it’s CAR T cells and engineering CAR T cells in novel ways for solid tumors, or whether it’s provoking distinct types of responses by tickling various ‘on’ and ‘off’ switches in the immune system using other kinds of immunological drugs. I think we’re going to see a lot of advances in those areas soon. Third, I think what’s become very exciting is this concept of interception which has taken on new expectations and new opportunities to intervene earlier and earlier in the cancer disease process. Hopefully, even before cancer has started, to prevent the development of cancer. The more we understand about the origins of certain types of cancers, and their immunological interactions, the more we can intervene early to prevent cancer from developing.

What might we be able to accomplish over the next 10 years?

I think in the next 10 years, we’re going to see more and more personalized immunotherapy taking advantage of being able to measure individual patients’ immune systems, and then matching immunotherapies to their own immune systems, rather than treating everybody like they’re the same. That’s going to be a major advance. We’ve seen some hints of that already, and we’re starting to understand how to use that more effectively. I think we’re going to see an explosion in cancer prevention, not just from interception, but also the ability to access the immune system, and perhaps other mechanisms to prevent cancer from developing, to react in earlier and earlier stages of those first changes that occur in cell types that could lead eventually to tumor progression. I think we’re also going to see more evidence of cures, and we’ve done very well in some cancers. Melanoma is probably one of the easiest places to look for great success in some leukemias and lymphomas. I think as we put immunotherapy earlier and earlier into our disease treatment courses, we’re going to see more and more cures in other kinds of diseases. That’s obviously great for patients, but it’s also going to reveal the places where we’re failing, and it’s going to reveal the types of biology that we still don’t understand. Along with that increasing rate of cures is going to be the recognition that not all patients are the same and not all tumors, even at the same tumor site type, have the same kind of interaction with the immune system or the rest of the body. Finally, I think we’re going to see an ability to thread the needle between immunotherapy and provoking adverse events such as autoimmunity. The more we can thread that needle, the more we’ll be able to treat patients more effectively.

What advice would you give to young scientists pursuing a career in cancer immunology and immunotherapy?

I think you have to love what you do, and you have to do what you love. It’s really important to find that passion, that thing that really inspires you to be thinking about the problem or thinking about the topic, even when you’re not at work. It’s the thing that you sort of can’t control but you get fixated on and just can’t wait to see how it turns out. My advice would be to follow your passion and look for the opportunities to enjoy science for science’s sake, and to make the discoveries for the sake of making the discoveries. I think it’s really important to do the important experiments, to focus on the questions and the problems that are really the big problems. If you do that, the basic science will take you to things that matter and have an impact. I just encourage people to focus on their passion and really stay committed to following their hearts about that.