CICON25 Reveals Bold New Strategies to Make Cancer Immunotherapy More Effective

The Ninth International Cancer Immunotherapy Conference (CICON25) wrapped up on September 12 in Utrecht, The Netherlands with some exciting developments in cancer immunotherapy.

The conference brought together researchers who are tackling some of the field’s biggest challenges, from understanding why certain tumors resist treatment to developing new ways to engineer immune responses. Here’s what stood out from the three days of presentations and discussions.

Aviv Regev, PhD, delivered the 2025 William B. Coley Award lecture, where she demonstrated how single-cell genomics combined with AI is transforming cancer research. Moving beyond the early days when researchers could only study tumors as bulk tissue samples – what she called “the lab equivalent of a fruit smoothie“, where everything is blended into one indistinguishable mix – her methods now separate out the pieces, profiling individual cells and mapping how they are spatially arranged within tumors.

Dr. Aviv Regev delivers the 2025 William B. Coley Award lecture at CICON25, following an introduction by CRI CEO Dr. Alicia Zhou. Dr. Regev will be formally honored with the award at CRI’s Annual Awards Gala on October 21, 2025. (All Photos: Fahad Benthani, PhD)

One striking example involved the discovery of a “T cell exclusion program” in melanoma. Her team analyzed melanoma tumors using single-cell RNA sequencing and identified a 248-gene program expressed by malignant cells that’s associated with keeping T cells out of tumors. Patients whose tumors had higher expression of this program before treatment showed worse outcomes with immunotherapy.

The breakthrough came when they predicted that CDK4/6 inhibitors – drugs that block key proteins controlling cell division – could suppress this exclusion program. When tested, the inhibitors not only reversed the program in cell models but also enhanced T cell-mediated killing and improved tumor control in animal models that were typically resistant to checkpoint inhibition. 

Dr. Regev also introduced several computational tools her lab has developed, including a method called “DIALOGUE”, which identifies multicellular programs where different cell types coordinate their gene expression, and “Perturb-Seq,” which combines CRISPR screens with single-cell RNA sequencing to systematically test how genetic perturbations affect cellular responses. Her team further developed AI methods like “SCHAF” (Single-Cell omics from Histology Analysis Framework), a tool that can generate single-cell expression data from simple histology images, potentially making advanced molecular profiling accessible for any patient with routine tissue samples.

Several CRI-funded scientists presented work that’s pushing the field forward in different directions.

Nicolas Kuhn, PhD, a CRI-Merck Postdoctoral Fellow, presents his research on how fibroblasts shape the tumor immune environment at CICON25.

Nicolas Kuhn, PhD, a CRI-Merck Postdoctoral Fellow, showed how local editing of fibroblasts in tumors changes their gene expression and alters the behavior of other immune cells. These stromal cells aren’t just sitting there passively – they’re actively influencing the immune landscape of tumors.

Michael Curran, PhD, a CRI WoodNext Foundation CLIP Investigator, presented data on bispecific antibodies that target both checkpoint pathways and tumor stroma simultaneously. It’s an approach that could be particularly useful for “cold” tumors that don’t naturally attract immune cells. 

Valsamo Anagnostou, MD, PhD, a Torrey Coast Foundation GEMINI CLIP Investigator, caught a lot of attention with her work on circulating tumor DNA. She’s developing blood tests that can monitor how well immunotherapy is working and even predict immune-related side effects before they become serious. This kind of real-time monitoring could help doctors adjust treatments more quickly and avoid unnecessary toxicity.

A few major themes emerged from the conference presentations. Spatial context is becoming increasingly important in understanding how tumors work. Where cells are located within a tumor, whether they’re near blood vessels, fibroblasts, or other cell types, can be just as important as what genes they express. Multiple research groups are using spatial genomics and proteomics to map these relationships.

The integration of different data types is another big trend. Researchers aren’t just doing RNA sequencing anymore. They’re layering on protein analysis, imaging data, perturbation experiments, and computational modeling. The challenge is making sense of all this information, which is where AI and machine learning tools are becoming essential.

Michael Curran, PhD, a CRI WoodNext Foundation CLIP Investigator, shares new research on bispecific antibodies designed to overcome “cold” tumors at CICON25.

Cold tumors remain one of immunotherapy’s biggest obstacles, but there were several presentations showing progress on this front. Talks highlighted how fibroblasts, macrophages, and other stromal cells in the tumor microenvironment actively shape resistance to immune infiltration. Researchers are developing strategies to recruit immune cells into these resistant tumors, including bispecific antibodies and engineered T cells designed to remodel the stroma and overcome these barriers.

The push toward more personalized approaches was evident throughout the conference. From neoantigen vaccines tailored to individual tumors to biomarkers that can predict which patients will respond to specific treatments, the field is moving away from one-size-fits-all approaches. This precision medicine angle could help more patients benefit from immunotherapy while reducing unnecessary side effects.

For patients and families, these developments are encouraging. Better diagnostic tools mean treatment decisions can be more informed and adjusted more quickly. New therapeutic approaches are emerging for cancers that have been particularly difficult to treat with existing immunotherapies. The combination of different treatment modalities, such as immunotherapy together with targeted drugs and stroma-modulating strategies, is opening possibilities that didn’t exist even a few years ago.

CICON25 was a meeting where many pieces are starting to come together. The technology for understanding tumors at the cellular level exists. AI tools are getting better at making sense of complex biological data. New therapeutic approaches are moving from preclinical models toward clinical trials. The field seems to be at a point where some of the long-standing challenges in cancer immunotherapy might finally have solutions.

The research presented at CICON25 reinforces that cancer treatment is becoming more sophisticated and more precise. While challenges remain, the work by CRI-funded investigators and others suggests that more effective and less toxic cancer treatments are on the horizon.


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