New imaging method links cells' spatial organization to cancer outcomes
· Medical Xpressedited by Sadie Harley, reviewed by Robert Egan
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Tumors are not made up of cancer cells alone. They also contain immune cells and other support cells that interact within a complex ecosystem known as the tumor microenvironment. A doctoral thesis by Linglong Huang at the Karolinska Institutet's Department of Oncology-Pathology suggests that the spatial organization of cells in solid tumors may provide clinically relevant information about patient outcomes.
A key part of the work was the development of a new method for analyzing tissue images. Unlike conventional techniques, it does not require defining exact cell boundaries, a challenge for irregularly shaped cells such as fibroblasts. The approach can be used to analyze spatial patterns across different cell types and tissue contexts.
Using this method, researchers found that cells surrounding blood vessels in colorectal tumors were organized in distinct layers, and certain patterns were linked to poorer patient outcomes. The analyses also showed that macrophages, a type of immune cell, are not randomly distributed. By treating a static tissue section as a snapshot of an ongoing process, it was possible to reconstruct how macrophages disperse from blood vessels into the surrounding tissue. Some of these dispersal patterns were linked to shorter survival.
"Cancer research often focuses on which cells are present in a tumor. In this work, we were also interested in where the cells are located and how they are organized in space and over time," says Huang.
The research also included an analysis of more than 7,900 tumor images from 21 cancer types. The findings showed that how closely cells are packed together in a tumor is linked to patterns of gene activity.
Densely packed regions showed higher levels of activity in pathways linked to mechanical forces within the tissue, as well as a specific type of memory T cell. This suggests that the physical structure of a tumor may provide information about biological processes across different cancer types.
The thesis also explored how the tumor ecosystem changes when cancer returns after treatment. In a collaborative study of recurrent liver cancer, certain immune cells appeared to suppress the body's immune response instead of fighting the tumor. In mouse models, blocking a specific molecule disrupted this interaction and improved the response to immunotherapy.
Overall, the findings suggest that the spatial organization of cells within tumors contains biologically important information that may complement existing approaches to studying cancer. The work also resulted in a computational framework that can be used to analyze spatial patterns in tumor tissues more generally.
The research was carried out in collaboration with researchers at Karolinska Institutet, Uppsala University, Lund University and Fudan University.
The doctoral work was supervised by professor Arne Östman. The public defense will take place on Oct. 23, 2026.
More information
Linglong Huang, Spatiotemporal dynamics of the TME-immune ecosystem in solid tumors, (2026). DOI: 10.69622/33349884
Key medical concepts
Tumor MicroenvironmentMacrophagesColorectal Neoplasms
Clinical categories
Oncology Provided by Karolinska Institutet Who's behind this story?
Sadie Harley
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