What is type-two immunity and how can it help in the fight against cancer? Why is it worth questioning established dogmas in science, and how can modern therapies be made accessible to everyone? These questions are discussed in a special interview with the winner of the 2025 Lem Prize, Prof. Li Tang from the École Polytechnique Fédérale de Lausanne (EPFL).

Michał Ciepielski: What led you to direct your research interests toward cancer immunotherapy?

Prof. Li Tang École Polytechnique Fédérale de Lausanne (EPFL): My research path has been an evolutionary journey, driven by both scientific curiosity and a persistent desire to develop more effective cancer treatments. I began my academic training in material science and nanotechnology during my bachelor's and PhD studies, focusing on engineering nanomaterials for targeted drug delivery to make therapies smarter and less toxic. However, I realized that even the most elegant delivery system is limited if the body's own defenses aren't empowered to finish the job.

That insight deepened during my postdoc training, where I first explored immunoengineering. Developing nanoparticle 'backpacks' to equip immune cells showed me the transformative potential of augmenting the immune system rather than bypassing it. I was captivated by a fundamental question: How can we engineer not just the tool, but the biology itself?

When I established my lab at EPFL, I committed to translating that vision. Cancer immunotherapy uniquely aligns with my core belief, that the most durable cures come from enabling the body's inherent intelligence. Unlike chemotherapy or radiotherapy, which attack tumors directly and often cause collateral damage to healthy tissue, immunotherapy works by stimulating the body's own immune system to recognize, adapt, and remember. It offers new hope where conventional treatments have limits. I am driven to leverage my research expertise to expand that hope to more patients by bridging advanced engineering and the power of the immune system, translating fundamental discoveries into tangible real-world impact.

The Lem Prize jury recognized your discoveries related to type 2 immunity. What does the “paradigm shift” in cancer immunotherapy, mentioned in your project title, actually involve?

For decades, cancer immunotherapy has been built on a type 1-centric framework—focused on Th1 cells, IFN-γ, and CD8+ T cells as the primary engines of anti-tumor immunity. Type 2 immunity, characterized by cytokines like IL-4, IL-5, and IL-13, was largely viewed through the lens of allergy or parasite defense, with controversial reports about its role in cancer.

Our recent work challenges that conventional view about type immunity. In collaboration with pioneers in CAR-T therapy, we found that in patients with acute lymphoblastic leukemia, a type 2 signature in the infused CAR-T product, not type 1, strongly correlated with ultra-long-term cancer-free survival beyond eight years. This was unexpected and prompted us to ask: Could type 2 signals actually support, rather than suppress, durable anti-tumor immunity?

We also tested this hypothesis mechanistically. Using an engineered IL-4 fusion protein (Fc–IL-4) alongside adoptive T-cell transfer in mouse models, we discovered that IL-4 directly reinvigorates exhausted CD8+ T cells by enhancing their function and persistence. This reveals a previously unappreciated synergy: type 2 cytokines can amplify the very type 1 responses that current therapies rely on.

So what does this shift involve? It's a move from viewing type 1 and type 2 immunity as opposing forces, to recognizing them as complementary partners. Instead of designing therapies that exclusively boost type 1 responses, we can now strategically integrate type 2 factors, such as IL-4, to enhance T-cell fitness, overcome exhaustion, and promote long-term memory.

This isn't about replacing the current paradigm; it's about refining it. By embracing the full spectrum of immune biology, we open new avenues to make immunotherapies more durable and effective for more patients. That's the translation I'm most excited to drive forward.

T lymphocytes and cytokines such as IL-4 and IL-10 have been known to science for many years. What in your research turned out to be the most surprising—also for your own team?

Molecules like IL-4 and IL-10 have been studied for decades. They have well-established roles in immune regulation and anti-inflammation. In the context of cancer, the prevailing assumption was that these cytokines as part of type 2 immunity could hinder an effective anti-tumor response. What surprised us and also challenged the assumptions was not what these molecules are, but how they function in cancer immunotherapy.

Our first surprise came from studying IL-10. Like many in the field, we initially associated IL-10 with immunosuppression. But when we investigated its role in T-cell metabolism, we discovered something unexpected: IL-10 could metabolically reprogram terminally exhausted CD8+ T cells, restoring their proliferation, killing capacity, and long-term persistence. Seeing these 'burnt-out' cells regain function through metabolic rewiring was a breakthrough moment for our team. The second surprise is the finding that a type 2 signature, specifically IL-4, supports long-term cancer-free survival as mentioned above. What tied these two surprises together was a unifying insight: certain type 2 cytokines (IL-10, IL-4), when delivered in the right context, can enhance, rather than inhibit, the type 1 responses that drive anti-tumor immunity. 

What tangible clinical effects could your discoveries have in the coming years, especially for cancer patients?

Our discoveries are already moving toward the clinic. Leman Biotech, an EPFL spin-off co-founded by me and my former postdoc, is commercializing metabolic cancer immunotherapy built on the core META 10 technology —IL-10–mediated metabolic reprogramming of T cells. The company has launched several investigator-initiated clinical trials (IITs) in China across hematologic malignancies, solid tumors, and autoimmune diseases. In relapsed/refractory B-ALL and DLBCL, its metabolically armored CD19 CAR-T achieved 100% complete remission in early clinical trials (20 patients) at doses as low as 1% of conventional CAR-T dosing, with excellent safety profile and minimal cytokine release syndrome. Longer term, we aim to integrate metabolic and/or type 2-enhancing strategies in multiple therapeutic modalities to potentially benefit more patients. 

Importantly, we are also developing more accessible cell therapies. A major barrier to widespread adoption of T-cell therapies is cost and complexity. Building on the ultra-low-dose potency and safety profile of metabolically armored CAR-T therapy, the company is developing an automated system that enables rapid ex vivo CAR-T production with higher quality and lower cost. If successful, this could make advanced immunotherapies accessible to a broader patient population, sooner—and in healthcare systems with limited resources.

You work at the intersection of biology, engineering, and medicine. What does day-to-day collaboration between scientists and clinicians look like, and how strongly does it influence the direction of your research?

For me, collaboration isn't an add-on—it's the engine that drives our research forward. My lab sits at EPFL, but we maintain deep, ongoing connections with scientists and clinical partners locally and worldwide. A typical collaboration involves joint problem-framing, shared data and samples, co-designed experiments with clear role definition, and iterative data review sessions. Such free, international collaboration is a key to the success of translational research I believe. 

The influence of collaboration on our research direction is profound and bidirectional. From clinic to lab: clinical problems help define our scientific questions. From lab to clinic: our mechanistic insights shape how the new therapies are engineered and future trials are designed.

Our IL-4 story is a perfect example of this cycle. On one hand, the observation came from clinical data—the unexpected correlation between type 2 signatures and long-term survival in CAR-T patients. Simultaneously, on the other hand, we asked the mechanistic question in lab: How does IL-4 as a typical type 2 cytokine work? Preclinical studies revealed it could directly reinvigorate exhausted CD8+ T cells. Now, that mechanistic insight motivates us to engineering next-generation immunotherapies that integrate type 1 and type 2 immunity for potentially enhanced clinical outcomes.

The Stanisław Lem European Scientific Award emphasizes vision and imagination in science. What role does imagination play in your research work?

For me, imagination in research is about seeing a reality that doesn't yet exist. It's the ability to look at established dogma and ask, 'But what if we're wrong?' It's the capacity to hold two disparate fields in your mind and envision a connection that no one has seen before.

In my lab, imagination plays a role at many stages of discovery. First, it helps us question the 'known', such as challenging the assumption that IL-10 and IL-4 are purely immunosuppressive. Second, it allows us to connect the unconnected, for example, linking type 2 cytokines to CD8+ T cell fitness. Third, it helps us visualize what we cannot yet see.

Looking ahead, imagination drives our long-term vision. Of course, imagination alone isn't enough. Every imaginative hypothesis must survive the discipline of experimentation, validation, and clinical testing. But without that initial spark—the willingness to wonder 'What if?'—we'd never challenge entrenched assumptions or explore uncharted territory.

Are you familiar with the literary work of Stanisław Lem? Are there any of his books that particularly stayed with you or proved useful in your life or academic career?

To be honest, I have not yet had the chance to read Stanisław Lem's literary work, a gap I sincerely hope to fill soon. However, I have watched the 1972 film Solaris, directed by the Russian master Andrei Tarkovsky. At its core, Solaris is not just a story about an alien ocean; it is a meditation on the limits of human understanding, the challenge of communicating with a system that operates by rules we do not yet comprehend, and the arrogance of assuming we can easily master what we do not understand. That theme has resonated with me throughout my research: to keep a humble mind toward the unknown and to avoid confining our thinking within preconceived assumptions.

 You are a young scientist who has already achieved international success. What do you consider to be the greatest challenge currently facing researchers working in cancer immunotherapy?

I am deeply grateful for that recognition, though I see my role less as having achieved international success and more as being privileged to work with brilliant mentors, colleagues, students, collaborators, clinicians, and the broader community. If I had to name one overarching challenge, it is this: making immunotherapies durably effective for a majority of patients, and accessible to all who need them.

On the biology side, we still struggle to overcome the barriers that limit long-term responses—especially in solid tumors. T-cell exhaustion, immunosuppressive microenvironments, and tumor heterogeneity mean that even powerful therapies like CAR-T or checkpoint inhibitors often work only for a subset of patients, or only temporarily. On the translation side, the complexity and high cost of developing new therapies remain formidable obstacles. A therapy that works in a top-tier academic center may never reach a patient in a resource-limited setting. 

What advice would you give to young researchers—including those from Wrocław Tech —who want to combine ambitious science with a real impact on people’s health and lives?

It’s my honor to offer some thoughts to young researchers and to anyone passionate about combining ambitious science with real impact. 

First, build depth before pursuing impact. Ambitious science must be grounded in rigor. Master your discipline—whether it is immunology, engineering, computational science, or clinical research. True innovation often comes from deep understanding, not from moving too quickly toward application.

Second, stay connected to real problems. If you want your work to impact people’s health and lives, spend time understanding patients’ needs, clinical realities, and unmet challenges. Let real-world constraints shape your scientific questions. 

Third, do not hesitate to cross boundaries. Many of today’s most transformative advances happen at the interface of fields. Combining ambitious science with real-world impact requires collaboration across disciplines, institutions, and countries. For young researchers at Wrocław Tech, this may mean leveraging strong engineering foundations while actively engaging with life sciences and medical partners.

Fourth, be patient and resilient. Translational science takes time. There will be setbacks, failed experiments, funding challenges, and skepticism. Impactful work is rarely linear. What matters is persistence and clarity of purpose.