The research integrates Carnegie Mellon’s expertise in expansion microscopy, a technique that physically enlarges and clears tissue samples to enhance resolution, with the Liu research team’s mesoscope, which is a fast, high-resolution imaging system. Combined, these tools allow scientists to observe tumor structures and cellular interactions in great detail.
“On our side, we are developing a new platform called mesoscope which is a very high throughput imaging technique that can capture a very large tissue area at high resolution,” explained Liu. “These two approaches combine our strengths with their strength.”
The NCI funding will accelerate work in the emerging field of spatial biology—an area focused on how spatial relationships between cell types within a tumor influence the progression of cancer and the resistance faced during treatment. Traditional pathology methods often rely on 2D slices of tissue, missing critical spatial context. Whereas Liu’s approach captures a fuller, three-dimensional view.
“A tumor is really a three-dimensional structure. This approach we are developing can image them in 3D,” said Liu. “That’s why I call this ‘3D tumor microenvironment’ and it can capture a much larger volume of the tissue.”
The goals of the project are divided into four main components. The team will:
- Upgrade their existing Omni Mesoscope to enable ultra high-throughput imaging
- Optimize tissue expansion protocols for thicker (about 1mm) tumor sections, while also labelling dozens of protein markers
- Automate the expansion and staining processes to increase reproducibility
- Apply the method to lung cancer animal models with differing responses to anti-PD-L1 immunotherapy.
“We are going to use an animal model. One model responds better to immunotherapy while the other one has resistance to immunotherapy,” Liu explained. “We’re going to compare how the immune microenvironment changes by looking at the structural changes in the three-dimensional space on cellular and subcellular level.”
The implications of this work are twofold. On the face of technology, it will deliver a powerful imaging platform capable of rapidly scanning whole tumor volumes at a 3D level. Biologically, it will shed light on how immune cells interact with tumor cells, leading to discoveries related to immune evasion in cancer.
“We are going to get more insight in terms of how the immune cells adapt and how the cancer cells evade the immune responses which is the immune evasion,” said Liu. “We are pretty excited to push the field forward.”
The project builds upon years of foundational work from both institutions. “They spent years developing expansion microscopy,” Liu shared. “On our side, the mesoscope also took years to build.”
With the support of NCI funding, the team is ready to connect new technology with essential medical questions about cancer.