Cracking the code of immune resistance in pancreatic cancer
A novel 3D co-culture platform reveals new insights into tumor–immune interactions
Pancreatic cancer is one of the most immunologically evasive and treatment-resistant malignancies, presenting major hurdles to the success of immune checkpoint inhibitors. While immune checkpoint inhibitors have transformed outcomes in several cancer types, they have shown limited success in pancreatic tumors, largely due to a highly suppressive tumor microenvironment that blocks effective T cell activity.
At AACR 2025, Aji Istadi, a PhD student at the Garvan Institute of Medical Research, will present a new approach to studying this resistance. Leveraging the RASTRUM™ Allegro platform, Aji and his team developed a 3D co-culture model that recreates key aspects of the pancreatic tumor microenvironment by incorporating cancer cells, fibroblasts, and T cells in a synthetic hydrogel matrix. This tunable model enables the study of tumor–immune interactions at high resolution and supports both live imaging and drug profiling.
Minisymposium: Modeling T cell and cancer cell interactions to examine immune checkpoint inhibition resistance in pancreatic cancer
Presenter: Aji Istadi, Garvan Institute of Medical Research
Abstract #3819
📅 Monday, April 28, 2025
🕝 2:30 PM – 4:30 PM
📍 Cancer Models: Mechanisms and Therapies Session | Room S401 - McCormick Place South (Level 4)
Revealing hidden interactions with 3D co-culture
Aji’s research is driven by a central question: how do pancreatic tumors block T cell responses, and how can we overcome it? His work focuses on understanding both cancer-intrinsic and extrinsic mechanisms of immune suppression, including the complex interactions between cancer cells, fibroblasts, and infiltrating immune cells.
“Pancreatic cancer is a particularly compelling disease to examine immunosuppression,” Aji explains, “given the extensive network of cancer-intrinsic and extrinsic mechanisms that sequester T cell responses. Only now, with the development of more sophisticated tools, are we able to dissect the intricate cell-to-cell and cell-to-environment interactions that underpin these pathways.”
Switching from 2D to 3D culture systems marked a turning point in the work. “Making the switch to 3D models was a crucial step—it revealed unique cellular interactions that were otherwise hidden in 2D,” says Aji. “Observing these dynamics in real time has been particularly exciting. Even subtle changes in environmental conditions can significantly alter cellular behaviour.”
The 3D cell model system he developed enables longitudinal live-cell imaging, allowing him to track T cell infiltration, migration, and engagement with cancer and stromal cells—offering a level of insight not possible in simpler models.
From insight to intervention
With the model established, Aji is now layering in single-cell RNA profiling to uncover the molecular signatures that shape immune dysfunction. Alongside this, he is performing immunomodulatory drug screening to pinpoint new targets and pathways that could enhance T cell responses.
“My research interest is in understanding how cancer cells evade anti-tumour T cell responses in pancreatic cancer,” he says, “with the goal of identifying therapeutically targetable vulnerabilities that increase the potency of immunotherapies.”
He’s also exploring how specific features of the matrix—such as stiffness or biochemical composition—impact cellular behavior. This ability to systematically vary the tumor microenvironment has opened up new biological questions and experimental possibilities.
Building more informative models for cancer research
As tools like spatial and single-cell analysis become more advanced, the need for models that reflect the complexity of real tumors has never been greater. Aji believes systems like this 3D co-culture are key to making those technologies more powerful and interpretable.
“With the rise of multi-omic and spatial characterisation technologies, we are beginning to reveal the intricacies of the tumour microenvironment,” he says. “However, many traditional models lack the complexity necessary to accurately reflect these environments. More approachable and accessible 3D culture systems present an exciting opportunity to increase the relevance of our models.”
By combining tunable 3D biology with advanced profiling tools, Aji’s work lays the foundation for a more predictive and scalable framework to study immune checkpoint inhibitor resistance and test new immunotherapies.
See the full study at AACR
If you’re investigating immune resistance, tumor biology, or immunotherapy development, Aji’s presentation offers a valuable opportunity to explore how engineered 3D models can reveal what standard systems miss—and open new doors in cancer research.
Minisymposium: Modeling T cell and cancer cell interactions to examine immune checkpoint inhibition resistance in pancreatic cancer
Presenter: Aji Istadi, Garvan Institute of Medical Research
Abstract #3819
📅 Monday, April 28
🕝 2:30 PM – 4:30 PM
📍 Cancer Models: Mechanisms and Therapies Session | Room S401 - McCormick Place South (Level 4)
Join the session to learn how 3D models are reshaping our understanding of tumor–immune interactions—and accelerating the next wave of immunotherapy innovation.
Learn more about Inventia Life Science's activities at AACR 2025 and explore how RASTRUM and RASTRUM Allegro can empower your cancer research with precise, tunable 3D models designed for discovery at scale.