Tumours 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 tumour microenvironment. A doctoral thesis by Linglong Huang at the Department of Oncology-Pathology suggests that the spatial organisation of cells in solid tumours may provide clinically relevant information about patient outcomes.
A key part of the work was the development of a new method for analysing 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 analyse spatial patterns across different cell types and tissue contexts.
Using this method, cells surrounding blood vessels in colorectal tumours were found to be organised 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.
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“Cancer research often focuses on which cells are present in a tumour. In this work, we were also interested in where the cells are located and how they are organised in space and over time,” says Linglong Huang .
The research also included an analysis of more than 7,900 tumour images from 21 cancer types. The findings showed that how closely cells are packed together in a tumour 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 type of specific memory T cells. This suggests that the physical structure of a tumour may provide information about biological processes across different cancer types.
The thesis also explored how the tumour 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 tumour. In mouse models, blocking a specific molecule disrupted this interaction and improved the response to immunotherapy.
Overall, the findings suggest that the spatial organisation of cells within tumours 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 analyse spatial patterns in tumour 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 defence will take place on 23 October 2026.
